ENDOCRINOLOGY – 2023

This 9-year-old girl presents with:

• Height below the 3rd percentile

• Significantly reduced growth velocity

• Delayed bone age (bone maturation is behind her chronological age)

• Normal intellect and no other systemic symptoms

These features strongly point toward Growth Hormone (GH) deficiency, which results in:

• Poor linear growth

• Delayed skeletal maturation (bone age)

• Normal proportions (unlike some syndromic causes)

• Often normal birth weight and height, but decline in growth by 2–3 years of age

GH deficiency can be congenital or acquired and should be confirmed by GH stimulation testing and IGF-1 levels.

❌ Why the Other Options Are Incorrect

• Familial short stature
  Patients are short but have normal growth velocity and bone age matches chronological age.

• Constitutional delay
  Presents with delayed bone age but normal growth velocity — “late bloomers” who catch up eventually.

• Turner syndrome
  Can cause short stature in girls, but usually also presents with other features (webbed neck, wide-spaced nipples, primary amenorrhea). Also, genetic testing would confirm 45,X karyotype.

• Hypothyroidism
  Would also cause poor growth, but often includes fatigue, constipation, weight gain, and dry skin — not seen here.

This 60-year-old woman presents with:

• Irritability and lethargy

• Hypercalcemia (Ca²⁺ = 11.2 mg/dL)

• Low phosphate

• Elevated ALP (alkaline phosphatase)

This pattern is classic for primary hyperparathyroidism, where:

• PTH is inappropriately elevated despite high calcium

• PTH increases calcium by stimulating bone resorption, increasing renal reabsorption, and activating vitamin D

• Phosphate is low because PTH promotes phosphate excretion

• ALP rises due to increased bone turnover

➡️ Measuring serum PTH is the most specific next step to confirm the diagnosis.

❌ Why the Other Options Are Incorrect

• Bone X-ray
  May show subperiosteal bone resorption or osteitis fibrosa cystica, but it is not the first diagnostic step.

• LFTs
  ALP can be liver-derived, but elevated calcium + low phosphate points to bone/parathyroid etiology.

• UCE (Urea, Creatinine, Electrolytes)
  Helpful in assessing renal function, but won’t confirm parathyroid pathology.

• TSH
  Thyroid dysfunction doesn’t explain this calcium-phosphate pattern.

De Quervain thyroiditis (also called subacute granulomatous thyroiditis) is a self-limited, painful thyroid inflammation, often following a viral upper respiratory infection. It causes:

• Painful, tender thyroid

• Transient hyperthyroidism (from release of preformed T3/T4)

• Low TSH, high T3/T4 initially

• Followed by hypothyroidism, then recovery

The radioactive iodine uptake (RAIU) is decreased because the thyroid is not actively synthesizing hormones — it is merely leaking preformed hormone due to inflammation and follicular destruction.

❌ Why the Other Options Are Incorrect

• It is painless
  ❌ Incorrect — painful thyroid is a hallmark feature (unlike silent thyroiditis or Hashimoto’s).

• Anti-thyroid drugs are effective
  ❌ Incorrect — The hyperthyroidism is due to hormone leakage, not overproduction; anti-thyroid drugs (like methimazole) are not effective.

• It follows bacterial infection
  ❌ Incorrect — It usually follows a viral infection (e.g., Coxsackievirus, mumps, adenovirus).

• Increased RAIU
  ❌ Incorrect — RAIU is decreased, because the thyroid is not taking up iodine during the inflammatory phase.

Levothyroxine is a synthetic form of thyroxine (T4) used to treat hypothyroidism. While it’s essential to restore normal thyroid hormone levels, in certain conditions, particularly ischemic heart disease, caution is required.

In ischemic heart disease (IHD) — such as angina or post-myocardial infarction — thyroid hormones can increase myocardial oxygen demand by:

• Raising heart rate

• Increasing contractility

• Raising metabolic rate

Starting full-dose levothyroxine in such patients can precipitate angina, arrhythmias, or even heart failure.
➡️ Dose should be started low and titrated slowly under cardiac monitoring.

❌ Why the Other Options Are Incorrect

• Neurological disorders
  These don’t generally require dose reduction unless there’s an elderly patient with comorbidities.

• Respiratory disorders
  Thyroid hormone doesn’t directly worsen most respiratory diseases; no routine dose reduction needed.

• Hematological disorders
  These may result from hypothyroidism (e.g., anemia), but don’t warrant reduced levothyroxine dosing.

• All of these
  Incorrect — only ischemic heart disease clearly necessitates a lower starting dose.

This 60-year-old woman has:

• A retrosternal goiter (thyroid enlargement extending behind the sternum)

• Dyspnea (difficulty breathing) and stridor (upper airway obstruction sound)

• A normal thyroid function test (euthyroid)

The presence of compressive symptoms (e.g., airway obstruction, stridor) in a non-toxic multinodular goiter (NKCM) is an absolute indication for surgery, even if thyroid function is normal.

➡️ The definitive treatment is total thyroidectomy, which:

• Relieves tracheal compression

• Prevents further growth or future complications

• Eliminates recurrence risk in multinodular goiter

❌ Why the Other Options Are Incorrect

• Radioactive iodine (RAI)
  Not effective for large or retrosternal goiters, especially with compressive symptoms. RAI is more suitable for toxic goiters or hyperthyroidism.

• Anti-thyroid drugs
  Used for hyperthyroidism, not for structurally compressive, euthyroid goiters.

• Steroids
  May reduce inflammation, not goiter size. Not appropriate for mechanical obstruction.

• Beta-blockers
  Provide symptomatic relief in hyperthyroidism (e.g., palpitations), but irrelevant here.

In Diabetic Ketoacidosis (DKA), patients typically present with:

• Severe dehydration

• Electrolyte imbalances

• Metabolic acidosis

• Marked hyperglycemia

In this case, the patient has profound hyponatremia (Na⁺ = 106 mmol/L), which requires careful correction.

The first-line fluid in DKA is always isotonic saline (0.9% NaCl or normal saline) because it:

• Expands intravascular volume

• Begins correcting sodium and fluid deficits

• Supports renal perfusion, aiding in clearance of glucose and ketones

Once glucose drops to ~200 mg/dL, 5% dextrose is added to prevent hypoglycemia while continuing insulin.

❌ Why the Other Options Are Incorrect

• 3% saline
  Hypertonic and used only for symptomatic severe hyponatremia (e.g., seizures, coma). DKA management does not start with 3% saline.

• 5% Dextrose
  Not used initially — added later once blood glucose drops to prevent hypoglycemia.

• Hypotonic saline
  Can worsen hyponatremia and lead to cerebral edema — contraindicated in this setting.

• Ringer’s lactate
  Contains lactate, which can confound acidosis management in DKA.

The first and most essential step in evaluating amenorrhea, especially in a woman of reproductive age, is to rule out pregnancy — regardless of the history.

Even though the husband reportedly has azoospermia, the couple already has two children, meaning prior fertility, and laboratory errors or misdiagnosis in azoospermia are possible.

Additionally, prolactin levels can rise during pregnancy — and a level of 400 ng/mL is within the typical range seen in pregnancy, though also elevated in prolactinomas.

But before jumping to imaging or invasive workup, the most logical and cost-effective step is to check for pregnancy.

❌ Why the Other Options Are Incorrect at This Stage

• Repeat husband’s semen analysis
  Not relevant in the acute evaluation of the woman’s amenorrhea — and she has already conceived before.

• MRI abdomen and pelvis
  Not indicated unless you suspect structural abnormalities (e.g., masses); not first-line for amenorrhea.

• MRI pituitary
  Could be needed if pregnancy is excluded and prolactin remains high — but not before ruling out the most common cause of elevated prolactin: pregnancy.

• Ultrasound abdomen and pelvis
  May help assess uterus and ovaries, but urine/blood pregnancy test is simpler and more direct.

Hypopituitarism is the deficiency of one or more anterior pituitary hormones, which includes:

• FSH and LH (gonadotropins)

• ACTH

• TSH

• GH

• Prolactin (may decrease or stay normal depending on cause)

When the pituitary fails, it leads to low levels of trophic hormones, including FSH and LH, resulting in:

• Amenorrhea or infertility

• Loss of secondary sexual characteristics

• Reduced libido

So, in hypopituitarism, FSH and LH are both low, along with other pituitary hormones.

❌ Why the Other Options Are Incorrect

• No change in prolactin levels
  Prolactin can decrease in hypopituitarism, especially with global pituitary failure.

• High FSH and LH
  Seen in primary gonadal failure, not pituitary failure.

• Increased ACTH
  ACTH is typically low, leading to secondary adrenal insufficiency.

• Low FSH, high LH
  This pattern is not seen in hypopituitarism — it would suggest some form of partial gonadotropin dysregulation, not pan-hypopituitarism.

This young woman presents with:

• Menstrual irregularities

• Galactorrhea (milk discharge without pregnancy)

• Low libido

• Headache and visual field defects

• Markedly elevated prolactin level (800 ng/mL)

These are classic signs of a prolactinoma — a prolactin-secreting pituitary adenoma, likely macroadenoma given the visual symptoms.

First-line treatment for prolactinomas is a dopamine agonist, such as bromocriptine or cabergoline. Dopamine inhibits prolactin secretion from the pituitary.

Bromocriptine:

• Lowers prolactin levels

• Shrinks tumor size

• Often restores normal menstruation and fertility

Surgery is reserved for cases unresponsive to medical therapy or with acute visual deterioration.

❌ Why the Other Options Are Incorrect

• Observation alone
  Not appropriate — prolactin is very high and patient has symptomatic mass effect (vision changes).

• Transsphenoidal pituitary resection
  Considered second-line if medical therapy fails or if tumor is compressing optic chiasm severely.

• Glucagon
  Has no role in prolactinoma treatment.

• Somatostatin
  Inhibits GH and other hormones, but is not effective for prolactinomas.

This 30-year-old patient presents with:

• Significant weight loss

• Fatigue, polyuria, polydipsia

• Elevated blood glucose

These features are classic for new-onset Type 1 Diabetes Mellitus (T1DM) or possibly severe Type 2 with catabolic features. In either case, the presence of weight loss and symptoms of hyperglycemia suggests insulin deficiency, and immediate insulin therapy is required to:

• Reverse the catabolic state

• Prevent diabetic ketoacidosis (DKA)

• Normalize blood glucose levels

Delaying insulin in such patients can lead to dangerous metabolic complications.

❌ Why the Other Options Are Incorrect

• GLP-1 receptor agonists
  Used in Type 2 diabetes, particularly with obesity — not first-line in symptomatic, likely insulin-deficient patients.

• Glyburide (sulfonylurea)
  Stimulates insulin secretion — ineffective if β-cell function is significantly compromised (as in Type 1).

• Thiazolidinediones
  Improve insulin sensitivity but act too slowly and are not suitable for acute or symptomatic hyperglycemia.

• Metformin
  First-line in stable Type 2 diabetes, but contraindicated in acute illness or significant weight loss until insulin stabilizes the patient.

Oligomenorrhea refers to infrequent or irregular menstrual cycles, typically defined as menstrual intervals longer than 35 days. It can result from various causes such as PCOS, thyroid disorders, hyperprolactinemia, or hypothalamic dysfunction.

When evaluating a patient, management depends on the underlying cause, but the basic treatment for regulating cycles and ensuring endometrial protection is:

➡️ Cyclical progesterone — administered for 10–14 days every 1–2 months:

• Induces regular withdrawal bleeding

• Prevents endometrial hyperplasia, which can occur due to unopposed estrogen in anovulatory women

❌ Why the Other Options Are Incorrect

• None of these
  Incorrect — untreated oligomenorrhea can lead to infertility and endometrial hyperplasia.

• Metformin
  Helpful in PCOS with insulin resistance, but not the first-line treatment for cycle regulation.

• COCPs (Combined oral contraceptive pills)
  Often used for hormonal regulation, acne, and contraception, but cyclical progesterone is preferred when the goal is just to induce regular shedding without contraception.

• Cyproterone acetate
  An anti-androgen, used in hirsutism and severe acne; not first-line for simple oligomenorrhea.

In pregnant women with Graves’ disease, antithyroid medications are required to control maternal hyperthyroidism, which can lead to miscarriage, preterm labor, and fetal hyperthyroidism if untreated.

Propylthiouracil (PTU) is the drug of choice during the first trimester of pregnancy because:

• It inhibits thyroid hormone synthesis and also peripheral conversion of T4 to T3

• It carries a lower risk of teratogenic effects compared to carbimazole or methimazole

After the first trimester, therapy may be switched to methimazole due to PTU’s potential for hepatotoxicity.

❌ Why the Other Options Are Incorrect

• Carbimazole
  Associated with congenital malformations (e.g., aplasia cutis, choanal/esophageal atresia) if used in the first trimester.

• Phenytoin
  An anticonvulsant, not used in thyroid disorders.

• Iodine
  Can suppress thyroid hormone temporarily but is not safe in pregnancy due to risk of fetal goiter and hypothyroidism.

• Beta blocker
  May be used for symptomatic relief (e.g., propranolol for tremor, tachycardia), but it does not treat the underlying hormone excess.

This patient presents with:

• Weakness, lethargy, and weight loss

• Hyponatremia (low sodium)

• Hypocalcemia (less specific, but sometimes seen in chronic illness or adrenal insufficiency)

These features raise suspicion for primary adrenal insufficiency (Addison’s disease), where the adrenal glands fail to produce adequate cortisol (and often aldosterone).

The Synacthen test (also called the ACTH stimulation test) is the gold standard for diagnosing adrenal insufficiency. It involves:

1. Giving synthetic ACTH (Synacthen)

2. Measuring cortisol response after 30–60 minutes

• In normal individuals, cortisol levels rise appropriately.

• In primary adrenal insufficiency, cortisol fails to rise due to adrenal failure.

❌ Why the Other Options Are Incorrect

• OGTT (Oral Glucose Tolerance Test)
  Used to diagnose diabetes, not relevant here.

• TSH
  Evaluates thyroid function. Hypothyroidism may cause lethargy, but not hyponatremia + weight loss together with hypocalcemia.

• Dexamethasone suppression test
  Used to diagnose Cushing’s syndrome (cortisol excess), not deficiency.

• PTH
  Would help evaluate calcium abnormalities, but hypocalcemia here is likely secondary to chronic illness or cortisol deficiency — and wouldn’t explain all symptoms.

In diabetic ketoacidosis (DKA), the most immediate concern is the patient’s acid-base balance and electrolyte status — not long-term glucose control.

Arterial Blood Gases (ABGs) provide rapid and crucial information on:

• Severity of metabolic acidosis (low pH, low HCO₃⁻)

• Compensatory respiratory response (low pCO₂)

• Overall clinical urgency

This guides fluid resuscitation, insulin therapy, and electrolyte replacement, especially potassium.

❌ Why the Other Options Are Incorrect Initially

• CBC
  May be useful later to rule out infection, but not urgent for DKA management.

• UCE (Urea, Creatinine, Electrolytes)
  Important but not as immediate as ABG — typically ordered alongside ABG.

• HbA1c
  Reflects long-term glucose control, not useful in acute settings.

• Random Blood Sugar (RBS)
  Confirms hyperglycemia, but diagnosis of DKA also requires acidosis and ketones — ABG is essential.

Empagliflozin is a member of the SGLT2 inhibitor class of antidiabetic drugs.

• It works by blocking the SGLT2 transporter in the proximal renal tubules, reducing glucose reabsorption.

• This leads to increased urinary glucose excretion, thereby lowering blood glucose levels.

• It also provides cardiovascular and renal benefits, making it especially useful in patients with diabetes, heart failure, or chronic kidney disease.

❌ Why the Other Options Are Incorrect

• DPP-4 inhibitor
  (e.g., sitagliptin) — increases incretin levels by preventing their degradation.

• GLP-1 agonist
  (e.g., liraglutide) — mimics incretin hormone, enhancing insulin secretion and reducing appetite.

• Biguanides
  (e.g., metformin) — reduce hepatic gluconeogenesis and increase insulin sensitivity.

• SGLT1 inhibitor
  Primarily affects glucose absorption in the gut, not the kidney; empagliflozin is SGLT2-selective.

This patient has:

• A T-score of -1.8 → osteopenia, not osteoporosis (osteoporosis = T ≤ -2.5)

• A history of oral steroid use for COPD, which significantly increases her risk for fragility fractures

Glucocorticoid-induced bone loss is a serious concern even before T-score reaches -2.5, especially if:

• The patient is older than 65

• The patient is expected to be on steroids ≥3 months

Alendronate, a bisphosphonate, is the first-line treatment in this setting. It:

• Inhibits osteoclast-mediated bone resorption

• Helps preserve bone density

• Reduces vertebral and hip fracture risk

❌ Why the Other Options Are Less Appropriate Alone

• Calcium and vitamin D supplements
  Essential for baseline bone health, but not sufficient alone to prevent fracture in glucocorticoid-induced osteopenia.

• Abaloparatide
  A PTH analog, used for severe osteoporosis. Not first-line in osteopenia with moderate risk.

• Raloxifene
  A SERM used primarily in postmenopausal women with osteoporosis and low breast cancer risk — less effective in steroid-induced cases.

• All of these
  Overly broad; Alendronate is the best single answer per current guidelines.

Hypertriglyceridemia is a well-known and important cause of acute pancreatitis, especially when triglyceride levels exceed 1000 mg/dL.

Mechanism:

• Excess triglycerides are broken down by pancreatic lipase into free fatty acids.

• These free fatty acids are toxic to pancreatic acinar cells, causing inflammation, necrosis, and pancreatitis.

• Hypertriglyceridemia is the third most common cause of acute pancreatitis after gallstones and alcohol.

❌ Why the Other Options Are Incorrect

• Diabetic foot
  Related to neuropathy, poor circulation, and infection — not directly caused by high triglycerides.

• Diabetes type 1
  Can be associated with ketoacidosis and other complications, but hypertriglyceridemia is more common in type 2 diabetes or secondary to insulin resistance.

• Appendicitis
  Caused by obstruction of the appendix, not related to lipid metabolism.

• Retinopathy
  Complication of long-standing hyperglycemia, not directly linked to triglyceride levels.

This patient has classic signs of Cushing syndrome, including:

• Weight gain, central obesity, buffalo hump

• Hypertension

• Proximal muscle weakness

• Osteoporosis with vertebral fracture

• Gynecomastia and testicular atrophy (due to hormonal imbalance)

Critically, his serum ACTH is low, which indicates that his Cushing syndrome is ACTH-independent — the source of excess cortisol is not the pituitary or ectopic ACTH, but from the adrenal gland itself.

The most likely cause is a cortisol-secreting adrenal adenoma or carcinoma, which:

• Raises cortisol levels

• Suppresses ACTH via negative feedback

• Leads to adrenal cortical hyperfunction and atrophy of the contralateral adrenal gland

A 10-cm adrenal mass is concerning for adrenal carcinoma, which can be functional and cause severe Cushing syndrome.

❌ Why the Other Options Are Incorrect

• Decreased radionuclide uptake in a thyroid gland nodule
  Related to thyroid disorders like a cold nodule; not related to cortisol or ACTH.

• Pulmonary 6-cm right hilar mass on chest radiograph
  Suggestive of small cell carcinoma producing ectopic ACTH — would cause high ACTH, not low.

• Sella turcica enlargement with erosion on head CT scan
  Seen in pituitary adenomas (Cushing disease) — which are ACTH-dependent and would show elevated ACTH, not low.

• Retroperitoneal 5-cm mass at the aortic bifurcation
  Suggestive of paraganglioma or lymphoma, not associated with cortisol production or Cushing syndrome.

This patient presents with:

• Polyuria and polydipsia

• History of head trauma

• Hypernatremia (Na⁺ 155 mmol/L)

• High serum osmolality (350 mOsm/kg)

• Very dilute urine (specific gravity 1.002)

These findings strongly indicate diabetes insipidus (DI) — specifically central diabetes insipidus, which occurs due to deficiency of antidiuretic hormone (ADH), often after head trauma or hypothalamic/pituitary injury.

ADH (vasopressin) is secreted by the posterior pituitary and acts on the collecting ducts of the kidney to promote water reabsorption. Without it, water is lost in urine, leading to:

• Dilute urine

• Hypernatremia

• Increased thirst and urination

❌ Why the Other Options Are Incorrect

• Melatonin
  Regulates sleep-wake cycles; has no role in fluid balance.

• Corticotrophin (ACTH)
  Regulates cortisol production — ACTH deficiency would cause hypotension, hyponatremia, not hypernatremia or dilute urine.

• Prolactin
  Affects lactation; unrelated to sodium or water balance.

• Oxytocin
  Involved in uterine contractions and milk let-down; not related to polyuria or osmolality.

This young woman presents with:

• Mild fasting hyperglycemia (120 mg/dL)

• Glucosuria without ketones or protein

• No insulin autoantibodies

• Strong family history (father had same condition at a young age)

These features are classic for MODY type 2 (Maturity-Onset Diabetes of the Young, type 2) — a monogenic, autosomal dominant form of mild, non-progressive hyperglycemia.

The most common mutation in MODY 2 is in the glucokinase (GCK) gene.
Glucokinase acts as a glucose sensor in pancreatic β-cells, triggering insulin release. A defective glucokinase results in a higher glucose threshold for insulin secretion → leading to mild, lifelong fasting hyperglycemia that rarely requires treatment.

❌ Why the Other Options Are Incorrect

• MHC DR
  Associated with type 1 diabetes mellitus, which involves autoimmune destruction of β-cells — not seen here.

• Glucagon
  Produced by α-cells of the pancreas; not involved in sensing blood glucose or causing MODY.

• Insulin
  Mutations in the insulin gene may cause MODY type 10, but it’s much rarer than GCK-MODY and usually more severe.

• GLUT4
  Insulin-dependent glucose transporter found in muscle and fat, not the pancreas. Mutations here would not cause this specific presentation.

This woman presents with:

• Galactorrhea (breast secretions)

• Amenorrhea (5 months without menstruation)

• A 0.7 cm pituitary mass (microadenoma)

These findings strongly suggest a prolactinoma, a prolactin-secreting pituitary adenoma.

Prolactin inhibits GnRH (gonadotropin-releasing hormone), which decreases LH and FSH secretion, leading to:

• Menstrual irregularities or amenorrhea

• Anovulation

• Infertility

So, infertility is the most likely additional complication.

❌ Why the Other Options Are Incorrect

• Hyperthyroidism
  Would present with weight loss, heat intolerance, tremors, tachycardia — none are seen here. Also, prolactin is not elevated in hyperthyroidism.

• Acromegaly
  Caused by GH-secreting pituitary adenoma, not prolactin. Presents with enlarged hands, coarse facial features, etc.

• SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion)
  Leads to hyponatremia and water retention, not galactorrhea or amenorrhea. It’s usually associated with hypothalamic or ectopic ADH secretion, not pituitary adenoma.

• Cushing’s disease
  Caused by ACTH-secreting pituitary adenoma, resulting in hypercortisolism — features like central obesity, striae, moon face would be present.

This patient with SLE on long-term corticosteroid therapy undergoes surgery and develops acute adrenal crisis postoperatively — presenting with:

• Hypotension

• Hyponatremia (Na⁺ 128)

• Hypoglycemia (glucose 52 mg/dL)

• Low CO₂ (metabolic acidosis)

• Normal-to-high K⁺ (4.9 mmol/L)

These are classic signs of acute adrenal insufficiency.

Long-term exogenous corticosteroids suppress ACTH secretion through negative feedback. This leads to adrenal cortical atrophy over time. In a stressful situation like surgery, the atrophied adrenals can’t mount a cortisol response, resulting in acute adrenal crisis.

❌ Why the Other Options Are Incorrect

• Bilateral cortical nodular hyperplasia
  Seen in ACTH-dependent Cushing disease (e.g., pituitary adenoma), not in steroid-suppressed patients.

• Solitary 1-cm adenoma without contralateral atrophy
  Suggests nonfunctioning or mildly active tumor — not relevant here. Adenomas that produce cortisol usually suppress the other adrenal (causing unilateral atrophy), not both.

• Bilateral hemorrhagic necrosis
  Characteristic of Waterhouse-Friderichsen syndrome — sudden adrenal failure due to sepsis (e.g., meningococcemia), which this patient does not have.

• Bilateral caseating granulomas
  Found in tuberculosis — a chronic cause of adrenal insufficiency, not acute post-op failure in a steroid-treated SLE patient.

The patient’s symptoms (painless, gradual, diffuse thyroid enlargement) and lab results (normal free T4, slightly increased TSH) point to Hashimoto’s thyroiditis. This is an autoimmune condition causing thyroid inflammation and often leading to subclinical hypothyroidism. Other options are less likely because:

• Papillary carcinoma usually presents as a single nodule.
• Diffuse nontoxic goiter typically lacks the TSH elevation seen here, suggesting an autoimmune cause.
• Toxic multinodular goiter causes hyperthyroidism (low TSH, high T4).
• Subacute granulomatous thyroiditis is typically painful and has a more acute onset.

This patient’s sudden death following a mild illness, combined with bilateral adrenal cortical hemorrhage, is characteristic of Waterhouse-Friderichsen syndrome — a rare but fatal complication of septicemia.

The most common cause of Waterhouse-Friderichsen syndrome is Neisseria meningitidis, a gram-negative diplococcus that can cause:

• Meningitis

• Meningococcemia (sepsis)

• DIC and adrenal hemorrhage, leading to acute adrenal insufficiency and shock

The presence of enlarged, hemorrhagic adrenal glands bilaterally at autopsy is a pathognomonic finding.

❌ Why the Other Options Are Incorrect

• Cytomegalovirus
  Can cause adrenal involvement in immunocompromised patients, but not sudden death with bilateral adrenal hemorrhage.

• Histoplasma capsulatum
  Fungal infection that can involve adrenals chronically, but not associated with sudden hemorrhage.

• Mycobacterium tuberculosis
  Causes chronic adrenal destruction (Addison’s disease), not acute hemorrhage or sudden death.

• Streptococcus pneumoniae
  Can cause meningitis, but rarely leads to Waterhouse-Friderichsen syndrome or adrenal hemorrhage.

This patient presents with:

• Elevated serum calcium (11.5 mg/dL)

• Low-normal phosphate (2.4 mg/dL)

• High-normal PTH (54 pg/mL)

These findings are classic for primary hyperparathyroidism, where PTH is inappropriately elevated for the level of calcium. Normally, high calcium should suppress PTH — so a “normal-high” PTH in the context of hypercalcemia is abnormal.

The most common cause of primary hyperparathyroidism is a parathyroid adenoma — a benign tumor of one parathyroid gland.

The radionuclear bone scan not showing uptake also suggests no widespread skeletal disease or metastatic cancer.

❌ Why the Other Options Are Incorrect

• Chronic renal failure
  Causes secondary hyperparathyroidism, with low calcium, high phosphate, and very high PTH due to phosphate retention and vitamin D deficiency.

• Hypervitaminosis D
  Causes hypercalcemia, but with low PTH due to feedback suppression. Also tends to cause high phosphate, not low.

• Parathyroid hyperplasia
  A cause of primary hyperparathyroidism, but usually all four glands are enlarged. It’s less common than adenoma and often part of MEN syndromes.

• Parathyroid carcinoma
  Rare; usually presents with severe hypercalcemia, very high PTH, and more aggressive symptoms like bone pain, fractures, and renal damage.

This patient has long-standing type 2 diabetes mellitus with multiple associated complications:

• Obesity (BMI = 30)

• Hyperglycemia (glucose 169 mg/dL)

• Diabetic nephropathy (elevated creatinine)

• Peripheral neuropathy (reduced pinprick/light touch sensation)

• Dyslipidemia (high triglycerides, low HDL)

• Cardiomegaly, indicating possible diabetic cardiomyopathy

• Now he has claudication — pain in the legs during exertion, which suggests peripheral artery disease (PAD)

Over time, PAD + neuropathy + poor glycemic control can lead to:

• Ischemia of lower extremities

• Non-healing ulcers

• Progression to gangrenous necrosis and possible limb amputation

This is a classic and devastating complication of advanced diabetes.

❌ Why the Other Options Are Incorrect

• Chronic pancreatitis
  More common in alcoholics and causes malabsorption and chronic pain, not linked directly to this diabetic progression.

• Systemic amyloidosis
  Can occur in chronic inflammatory or plasma cell diseases — but this patient has no signs of such conditions.

• Ketoacidosis
  More common in type 1 diabetes; this patient likely has type 2, and there’s no acute decompensation or metabolic acidosis mentioned.

• Hypoglycemic coma
  This patient is not on medications, especially insulin or sulfonylureas, which are the main causes of hypoglycemia. His glucose is actually elevated.

This patient presents with Cushing syndrome, suggested by:

• Weight gain, puffy face, abdominal striae, hypertension, glucose intolerance/diabetes, muscle weakness, easy bruising, and osteoporotic fractures

• Cortisol levels remain high throughout the day (normally, they decline by evening), indicating loss of diurnal variation — a hallmark of Cushing syndrome

To identify the cause, we differentiate between:

• ACTH-dependent causes: Pituitary adenoma (Cushing disease), ectopic ACTH (e.g., small-cell lung cancer)

• ACTH-independent causes: Adrenal adenoma, adrenal carcinoma, exogenous steroids

In this case:

• Persistent high cortisol

• Features consistent with Cushing syndrome

• No mention of elevated ACTH, and symptoms are not rapidly progressive or malignant-appearing (as in ectopic ACTH)

An adrenal adenoma secreting cortisol would:

• Suppress ACTH (via negative feedback)

• Cause atrophy of the contralateral adrenal cortex (due to lack of ACTH stimulation)

❌ Why the Other Options Are Incorrect

• Adenoma of the right adrenal cortex without atrophy of contralateral adrenal cortex
  This would not happen — ACTH suppression causes atrophy in the non-functioning adrenal.

• Corticotroph adenoma of the anterior pituitary, medullary carcinoma of thyroid, and bilateral nodular hyperplasia of the adrenal cortex
  Medullary thyroid carcinoma is associated with MEN syndromes, not Cushing syndrome.

• Corticotroph adenoma with bilateral hyperplasia
  Seen in Cushing disease, but would usually have elevated ACTH, not suppressed levels.

• Small-cell carcinoma of lung with bilateral hyperplasia
  Ectopic ACTH production leads to rapid onset, severe symptoms, and marked ACTH elevation — not consistent with this patient’s subacute presentation.

This patient presents with classic signs of hyperthyroidism:

• Weight loss, heat intolerance, increased appetite, tremor, tachycardia, and proptosis (exophthalmos)

• His TSH is suppressed, and radioiodine uptake is diffusely increased, indicating Graves disease

Graves disease is an autoimmune hyperthyroidism caused by TSH receptor–stimulating antibodies (TRAb). These antibodies stimulate the thyroid diffusely, causing:

• Hyperplasia of follicular epithelium

• Scalloped colloid due to increased uptake

• Papillary infoldings into follicular lumen

• Lymphoid aggregates in the stroma due to the autoimmune nature

❌ Why the Other Options Are Incorrect

• Nodules with nests of cells separated by hyaline stroma that stains with Congo red
  → Classic for medullary thyroid carcinoma with amyloid deposition, not Graves disease.

• Destruction of follicles, lymphoid aggregates, and Hurthle cell metaplasia
  → Seen in Hashimoto thyroiditis, a hypothyroid condition, not hyperthyroidism.

• Follicular destruction with inflammatory infiltrates containing giant cells
  → Suggestive of subacute granulomatous thyroiditis (De Quervain) — painful thyroid, often after viral illness.

• Enlarged thyroid follicles lined by flattened epithelial cells
  → Seen in colloid goiter, a non-toxic, euthyroid condition — not associated with autoimmune hyperthyroidism.

Somatostatin is a powerful inhibitory hormone secreted by the D cells of the pancreas and gastrointestinal tract. Its main role is to act as a brake on the digestive system.

It inhibits the release of multiple hormones, including:

• Secretin (stimulates pancreatic bicarbonate)

• Cholecystokinin (CCK) (stimulates gallbladder contraction and pancreatic enzyme secretion)

• Gastrin, insulin, glucagon, and others

By suppressing secretin and CCK, somatostatin slows digestion, reduces enzyme and bile secretion, and allows more time for nutrient absorption.

❌ Why the Other Options Are Incorrect

• Glucagon
  Primarily raises blood glucose levels; no significant inhibitory role on secretin or CCK.

• Aldosterone
  Regulates sodium and water balance via the kidney — unrelated to GI hormone regulation.

• Insulin
  Promotes glucose uptake; no role in inhibiting secretin or CCK.

• Growth hormone
  Regulates growth and metabolism; does not directly affect GI hormone secretion.

Glucagon is a water-soluble peptide hormone that acts primarily on hepatocytes (liver cells) to raise blood glucose levels during fasting or stress.

Since it can’t cross the cell membrane, it binds to a G protein–coupled receptor (GPCR) on the cell surface. This activates adenylyl cyclase, an enzyme that converts ATP into cyclic AMP (cAMP) — the key second messenger.

cAMP then activates protein kinase A (PKA), which triggers a phosphorylation cascade. This leads to:

• Glycogen breakdown (glycogenolysis)

• Inhibition of glycogen synthesis

• Stimulation of gluconeogenesis

Thus, cAMP is the classic second messenger for glucagon signaling.

❌ Why the Other Options Are Incorrect

• Cyclic GTP
  Second messenger for nitric oxide and ANP, not glucagon.

• Cyclic ATP
  Doesn’t exist — ATP is the precursor to cAMP.

• Cyclic GDP / Cyclic ADP
  Not known physiological second messengers in this context.

During starvation, the body shifts into a catabolic state to maintain blood glucose and provide energy. The sequence of changes includes:

1. Early fasting (first 24 hours):

   • Liver glycogen is broken down to maintain blood glucose.

   • Glycogen stores are depleted within ~24 hours.

2. Prolonged fasting/starvation:

   • Gluconeogenesis (from amino acids, lactate, glycerol) takes over.

   • Ketone bodies increase to fuel the brain.

   • Glucagon, epinephrine, and norepinephrine all rise to mobilize energy reserves.

Thus, glycogen levels decrease, not increase.

❌ Why the Other Options Are Correctly Increased

• Glucagon
  Increases to stimulate glycogenolysis and gluconeogenesis.

• Epinephrine
  Enhances lipolysis and supports glucose production during stress.

• Norepinephrine
  Supports sympathetic responses and promotes fat breakdown.

• Ketone bodies
  Increase significantly after 2–3 days of fasting to supply energy to the brain and muscles.

Cushing syndrome is caused by excess cortisol, either from endogenous overproduction (e.g., ACTH-secreting tumor, adrenal adenoma) or exogenous steroid use.

Cortisol has mineralocorticoid activity — it can bind aldosterone receptors in the kidney, promoting:

• Sodium retention → hypernatremia

• Water retention → hypertension

• Potassium excretion → hypokalemia

• Hydrogen ion loss → metabolic alkalosis

This explains the patient’s weight gain, muscle weakness, and central obesity. The thin limbs are due to protein catabolism, and purple striae from skin thinning and collagen breakdown.

❌ Why the Other Options Are Incorrect

• Potassium
  Usually decreased due to increased urinary loss (hypokalemia).

• Chloride
  Often decreased (due to metabolic alkalosis), not increased.

• Calcium
  Cortisol reduces calcium absorption → may lead to hypocalcemia, not hypercalcemia.

• Magnesium
  Not significantly altered in Cushing’s syndrome.

Thyroxine (T₄), once converted to the more active T₃, enters the target cell and binds to a nuclear receptor.

These thyroid hormone receptors are located inside the nucleus, where they bind to DNA response elements and regulate gene transcription. This changes the synthesis of proteins, affecting metabolism, growth, and development.

This mechanism is slow but long-lasting, typical of steroid and thyroid hormones — both use nuclear receptors because they are lipid-soluble.

❌ Why the Other Options Are Incorrect

• Stimulation of enzyme synthesis at ribosome level
  Happens after gene transcription is regulated — not the primary site of hormone action.

• Cell surface receptor
  Used by peptide hormones (e.g., insulin, epinephrine). Thyroxine is lipophilic and crosses membranes to act inside the cell.

• Direct activation at the enzyme level
  Characteristic of some signaling molecules, not thyroxine — which acts at the genetic transcription level.

• Interaction with nuclear chromatin
  Too vague and indirect — the actual mechanism is binding to a nuclear receptor, which then interacts with DNA.

Decreased glucose tolerance refers to a reduced ability of the body to handle glucose properly, especially after a glucose-rich meal or oral glucose tolerance test (OGTT). It means that:

• The body doesn’t clear glucose efficiently from the blood

• This results in higher-than-normal blood glucose levels after eating or glucose intake (i.e., postprandial hyperglycemia)

It’s often an early indicator of insulin resistance or pre-diabetes, and can precede type 2 diabetes.

❌ Why the Other Options Are Incorrect

• Decreased ability to absorb glucose from diet
  Glucose absorption from the gut is usually efficient and not the problem in glucose intolerance.

• Normal physiological response
  It’s not normal — it’s a sign of abnormal glucose regulation.

• Increased ability to absorb glucose from diet
  Again, absorption is not the issue; the problem is how the body processes glucose after it enters.

• Following a glucose load, the body responds by hypoglycemia
  Opposite of what happens in decreased glucose tolerance — blood sugar stays too high, not too low.

Urobilinogen is a normal breakdown product of hemoglobin metabolism.

Here’s how it works:

1. Hemoglobin → broken down in macrophages to bilirubin

2. Bilirubin → conjugated in liver → excreted into bile → reaches intestines

3. In intestines, it is converted by bacteria into urobilinogen

4. Some urobilinogen is reabsorbed into the bloodstream and excreted in urine — where it’s either colorless or oxidized to urobilin, giving urine its yellow color.

Thus, small amounts of urobilinogen in urine are normal.

❌ Why the Other Options Are Incorrect

• Stercobilin
  Gives stool its brown color; found in feces, not urine.

• Biliverdin
  Intermediate in heme breakdown, converted to bilirubin — not normally present in urine.

• Hemoglobin
  Should not appear in urine unless there is hemolysis or glomerular damage — a pathological finding.

• Bilirubin
  Conjugated bilirubin may appear in urine in liver disease or obstruction, but it’s not normally present in healthy individuals.

Growth hormone (GH) is secreted in a pulsatile manner from the anterior pituitary, regulated by a balance between stimulatory (GHRH) and inhibitory (somatostatin) signals.

Exercise is one of the most potent physiological stimuli of GH release. It increases GH to:

• Promote lipolysis

• Support muscle growth and repair

• Enhance glucose mobilization

The increase in metabolic demand and stress on muscles during exercise signals the hypothalamus to increase GHRH, leading to a surge in GH.

❌ Why the Other Options Are Incorrect

• Free fatty acids
  Elevated levels inhibit GH secretion, acting as a negative feedback signal.

• Somatostatin
  A GH-inhibiting hormone secreted by the hypothalamus — directly suppresses GH release.

• Hyperglycemia
  High blood sugar suppresses GH — the body does not need to mobilize more energy.

• Obesity
  Associated with chronically low GH levels due to persistent high insulin and fatty acids.

Down-regulation of receptors refers to a decrease in receptor number or sensitivity in response to excess hormone stimulation — a classic negative feedback mechanism to prevent overstimulation.

This is primarily achieved through internalization of receptors:

• After prolonged exposure to high hormone levels, receptors on the cell surface are endocytosed (pulled into the cell).

• Once inside, they are either recycled back to the membrane or degraded.

• This reduces the number of functional receptors on the surface, leading to reduced cellular response — even if hormone levels remain high.

❌ Why the Other Options Are Incorrect

• Chemical nature of receptor
  Determines how the receptor works, but does not regulate its down-regulation in response to hormone levels.

• Activation of receptor molecule
  Necessary for signaling, but does not cause down-regulation by itself.

• Synthesis of receptor
  Opposite of down-regulation — this refers to up-regulation or increased receptor availability.

• Binding of hormone to receptor
  Triggers activation, but down-regulation happens after prolonged binding and involves receptor internalization, not just binding itself.

During exercise, muscle cells need rapid energy, and the fastest, most immediate source of glucose is their own stored glycogen.

Muscle glycogenolysis breaks down glycogen into glucose-6-phosphate, which then enters glycolysis to produce ATP for muscle contraction. Importantly, muscles cannot export glucose (they lack glucose-6-phosphatase), so this glucose is used locally within the muscle.

This is the primary source of glucose during early and intense exercise.

❌ Why the Other Options Are Incorrect

• Protein breakdown
  Not a major source of glucose during exercise — it’s a last-resort energy source in prolonged starvation.

• Hepatic gluconeogenesis
  Generates glucose from lactate, amino acids, etc., but is slower and supports blood glucose levels, not immediate muscle energy.

• Lipolysis
  Provides fatty acids, not glucose. Muscles can use fats for energy, but this is slower and oxygen-dependent, not the primary source for quick glucose.

• Hepatic glycogenolysis
  Maintains blood glucose for the brain and other tissues — not the main glucose source inside the muscle

Catecholamines like norepinephrine and epinephrine act on adrenergic receptors (α and β) throughout the cardiovascular system.

Alpha-1 adrenergic receptors, located on vascular smooth muscle, are primarily responsible for vasoconstriction. When activated, they increase intracellular calcium, causing contraction of vascular smooth muscle → leading to increased peripheral resistance and blood pressure.

This vasoconstriction is mediated exclusively by alpha receptors, particularly α1 — not β receptors.

❌ Why the Other Options Are Incorrect

• Strength of vascular muscle contraction
  A vague option — if referring to the heart (myocardium), β1 receptors control contractility. If vascular smooth muscle, it’s still tone, not “strength” per se — and the correct interpretation is already covered by vasoconstriction.

• Blood flow to coronary arteries
  Regulated largely by local metabolic factors (e.g., adenosine, NO), not alpha receptors. Catecholamines may constrict coronary vessels via α, but β2-mediated vasodilation also plays a role — so not “alpha only.”

• Heart rate
  Controlled by β1 adrenergic receptors in the SA node — not alpha.

• Velocity of conduction in heart
  Controlled by β1 receptors in the AV node — not alpha.

This patient has mild fasting hyperglycemia that was first noticed during pregnancy (gestational diabetes) and has persisted postpartum. Her glucose is elevated but not diabetic-range, and it’s well-controlled with diet alone — this suggests a genetic form of mild hyperglycemia, most likely MODY (Maturity-Onset Diabetes of the Young) type 2, caused by glucokinase (GCK) deficiency.

Glucokinase acts as the glucose sensor in pancreatic β-cells. It catalyzes the phosphorylation of glucose to glucose-6-phosphate — the first step in glycolysis. Its reduced activity raises the threshold at which β-cells secrete insulin, so patients have mild fasting hyperglycemia, especially during metabolic stress (like pregnancy), but usually don’t develop severe diabetes.

❌ Why the Other Options Are Incorrect

• Lactate dehydrogenase
  Converts pyruvate to lactate — not involved in glucose sensing or regulation of insulin release.

• Enolase
  Converts 2-phosphoglycerate to phosphoenolpyruvate — a late glycolytic step, not rate-limiting or regulatory.

• Phosphofructokinase (PFK)
  Rate-limiting enzyme in glycolysis, but not involved in pancreatic glucose sensing. Its defect would affect energy metabolism broadly, not cause isolated hyperglycemia.

• Pyruvate kinase
  Catalyzes final step in glycolysis; deficiency leads to hemolytic anemia, not hyperglycemia.

This infant presents with floppiness, poor feeding, constipation, hypotonia, macroglossia, umbilical hernia, and lethargy — all classic signs of congenital hypothyroidism.

Thyroid hormone is essential for brain development, muscle tone, and metabolism. Deficiency in infancy causes:

• Lethargy, minimal crying (“good baby”)

• Hypotonia (“floppy baby”)

• Constipation (tiny pellet stools)

• Macroglossia (big tongue)

• Delayed milestones, umbilical hernia

• Prolonged jaundice (often present earlier)

Early diagnosis is critical, as untreated congenital hypothyroidism leads to irreversible intellectual disability. That’s why newborn screening is done universally in many countries.

❌ Why the Other Options Are Incorrect

• Down syndrome
  May have hypotonia and umbilical hernia, but wouldn’t explain constipation, sleepiness, macroglossia, or feeding difficulty at this level. Also, there’s no mention of dysmorphic facial features, simian crease, or poor Moro reflex.

• Addison’s disease
  Rare in infants and presents with hyperpigmentation, vomiting, low sodium, low BP — not a “good baby” or macroglossia.

• Botulism
  Causes floppy baby syndrome, but typically in the U.S. it’s associated with honey exposure or contaminated food. The onset is acute, not slow and progressive, and doesn’t cause macroglossia or hernia.

• Galactosemia
  Presents in newborns with vomiting, jaundice, hepatomegaly, and E. coli sepsis — not hypotonia with macroglossia and hernia.

In pancreatic beta cells, glucose entry is crucial for sensing blood glucose levels and triggering insulin secretion.

The transporter responsible is GLUT-2 — a low-affinity, high-capacity glucose transporter. This means it only becomes active when blood glucose is high, making it ideal for a “glucose sensor.”

Once glucose enters via GLUT-2, it is metabolized to increase ATP, which closes K⁺ channels, depolarizes the membrane, opens Ca²⁺ channels, and leads to insulin release.

In hypoglycemia, GLUT-2 allows less glucose into the cell due to its low affinity, so insulin is not secreted — which is exactly what the body wants during low blood sugar.

❌ Why the Other Options Are Incorrect

• GLUT-4
  Found in muscle and adipose tissue; insulin-dependent. Not present in beta cells.

• GLUT-3
  Found in neurons; high affinity — helps brain take up glucose even during hypoglycemia.

• GLUT-5
  Transports fructose, not glucose.

• GLUT-1
  Found in RBCs and the blood-brain barrier; high-affinity transporter, not the main one in beta cells.

Catecholamines like epinephrine and norepinephrine stimulate lipolysis — the breakdown of triglycerides into free fatty acids — to provide energy, especially during stress or fasting.

This lipolytic effect is primarily mediated through β3 adrenergic receptors found on adipose tissue. When stimulated, they activate adenylyl cyclase, increase cAMP, and activate hormone-sensitive lipase (HSL), which breaks down fat.

❌ Why the Other Options Are Incorrect

• β1 adrenergic receptors
  Mainly found in the heart; they increase heart rate and contractility, not fat breakdown.

• β2 adrenergic receptors
  Involved in smooth muscle relaxation (e.g., bronchodilation), not the main mediators of lipolysis.

• α1 adrenergic receptors
  Mediate vasoconstriction and smooth muscle contraction — not involved in lipolysis.

• α2 adrenergic receptors
  Actually inhibit lipolysis by reducing cAMP levels, opposing β-receptor activity.

Acromegaly is caused by excess growth hormone (GH) secretion, usually from a pituitary adenoma. This leads to elevated insulin-like growth factor 1 (IGF-1), causing the characteristic symptoms: enlarged hands/feet, coarse facial features, organomegaly, and metabolic disturbances.

To treat it, we need to reduce GH secretion.

Somatostatin (also called growth hormone–inhibiting hormone) is a hypothalamic hormone that inhibits the anterior pituitary from releasing GH. Synthetic analogs like octreotide are used clinically to control GH levels and shrink tumors.

❌ Why the Other Options Are Incorrect

• GHRH
  Stimulates GH release — would worsen acromegaly.

• Glucocorticoid
  Has no direct inhibitory effect on GH or IGF-1 in this context; not a treatment for acromegaly.

• Growth hormone
  Giving more GH in a condition already caused by excess GH would exacerbate symptoms.

• Insulin
  May be affected by GH excess (due to insulin resistance), but insulin itself doesn’t treat the underlying cause.

This woman has galactorrhea and absent menstruation 6 months after giving birth, despite not breastfeeding. That’s not a normal postpartum state.

The hormone prolactin stimulates milk production and suppresses GnRH, which stops ovulation and menstruation. Since she isn’t nursing, ongoing high prolactin is abnormal — likely from a pituitary cause like a prolactinoma.

❌ Why the Other Options Are Wrong

• Normal postpartum response
  Not normal at 6 months without breastfeeding.

• Increased dopamine synthesis
  Dopamine inhibits prolactin — it would reduce, not raise, it.

• Insufficient TSH secretion
  This would not cause high prolactin. Hypothyroidism may increase prolactin, but only when TRH is elevated, not when TSH is low.

• Reduced growth hormone secretion
  GH has no role in lactation or menstrual cycles.

• Total plasma calcium consists of:

  • ~50% free, ionized Ca²⁺ → biologically active form

  • ~40% bound to plasma proteins (mainly albumin)

  • ~10% complexed with anions (bicarbonate, phosphate, citrate)

• The ionized form (50%) is responsible for all physiological actions:

  • Muscle contraction

  • Nerve conduction

  • Hormone secretion

  • Blood clotting

Why the other options are incorrect:

• 25%: Too low — ionized calcium is about 50%, not 25%.

• 1%: Far too low.

• 100%: Total plasma calcium is partly bound — not all is free.

• 60%: Slight overestimate — ionized fraction is about 50%.

• ACTH is secreted by the anterior pituitary to stimulate cortisol production.

• Long-term use of exogenous glucocorticoids leads to negative feedback on the hypothalamus and pituitary → decreased ACTH secretion.

• This may result in secondary adrenal insufficiency if glucocorticoids are withdrawn suddenly.

Why the other options are incorrect:

• Stress increases CRH → increased ACTH.

• Pituitary adenoma usually causes increased ACTH (if ACTH-secreting).

• Low serum glucocorticoid would stimulate ACTH release, not decrease it.

• In primary adrenal insufficiency, low cortisol triggers high ACTH (compensatory rise).

• High TSH + Low T4 = Primary hypothyroidism → thyroid gland is failing, so pituitary increases TSH to compensate.

• Autoimmune thyroid disease (Hashimoto thyroiditis) is the most common cause of hypothyroidism in this setting — even without palpable thyroid.

• Symptoms (fatigue, weight gain, myalgias, numbness) also fit hypothyroidism.

Why the other options are incorrect:

• Hyperthyroidism → would show low TSH + high T4 — opposite of this case.

• Iodine deficiency → rare in developed countries; patient has no signs of endemic goiter.

• Hyperthyroidism secondary to hypothalamic-pituitary defect → hyperthyroidism would show low TSH + high T4 — not the case.

• Hypothyroidism secondary to hypothalamic-pituitary defect → in central hypothyroidism, TSH would be low or inappropriately normal, not elevated.

• Aldosterone is released in response to:

  • Low blood pressure

  • Low sodium

  • High potassium

  • Increased renin → angiotensin II → stimulates aldosterone.

• If mean arterial blood pressure rises, the renin-angiotensin-aldosterone system (RAAS) is suppressed → less aldosterone is released.

Why the other options are incorrect:

• Decreased Na⁺ at macula densa: Stimulates renin → aldosterone.

• Rise in serum potassium: Directly stimulates aldosterone to promote K⁺ excretion.

• Increased renin secretion: Leads to more aldosterone.

• Fall in mean arterial BP: Stimulates RAAS → more aldosterone.

• Aldosterone is a mineralocorticoid secreted by the zona glomerulosa (outer layer of adrenal cortex).

• It acts on the kidneys to:

  • Increase sodium and water reabsorption

  • Increase blood volume

  • Raise blood pressure

• It is the key hormone in adrenal regulation of long-term blood pressure — through volume control.

Why the other options are incorrect:

• Epinephrine (medulla):

  • Increases cardiac output and peripheral resistance temporarily, but not the main BP regulator from adrenal gland — more short-term effect.

• Norepinephrine (adrenal cortex):

  • Incorrect — norepinephrine is released from medulla, not cortex.

• Cortisol (zona fasciculata):

  • Has permissive effects on vasculature but is not the primary BP hormone.

• Testosterone (zona reticularis):

  • No direct role in blood pressure regulation.

• The anterior pituitary (adenohypophysis) develops from an upward growth of oral ectoderm, called Rathke’s pouch.

• Rathke’s pouch detaches from the roof of the mouth and forms the anterior pituitary.

• The posterior pituitary comes from neuroectoderm — extension of the hypothalamus.

Why the other options are incorrect:

• Mesoderm: Does not contribute to the pituitary gland.

• Neuroectoderm: Forms posterior pituitary, not anterior.

• Oral endoderm: Incorrect — ectoderm, not endoderm, forms anterior pituitary.

• Trophoblast: Forms placenta, not involved in pituitary development.

• The adrenal gland has two parts:

  • Cortex → from mesoderm (coelomic mesothelium)

  • Medulla → from neural crest cells

• Chromaffin cells of the adrenal medulla (which secrete catecholamines like adrenaline and noradrenaline) are derived from neural crest cells.

• These migrating neural crest cells infiltrate the developing adrenal cortex to form the medulla.

Why the other options are incorrect:

• Notochord: Forms axial structures, not involved in adrenal development.

• Endoderm: Forms gut and associated organs, not adrenal medulla.

• Coelomic mesothelium: Forms adrenal cortex, not chromaffin cells.

• Splanchnic mesoderm: Forms heart, blood vessels, and gut connective tissue — not chromaffin cells.

• The thyroid gland develops from a midline endodermal thickening in the floor of the primitive pharynx — at the foramen cecum.

• It then descends into the neck to form the thyroid gland.

• This explains why thyroglossal duct remnants can be found along this path.

Why the other options are incorrect:

• Dorsal bud: Refers to the pancreas, not thyroid.

• Third pharyngeal pouch: Gives rise to inferior parathyroids and thymus, not thyroid.

• First pharyngeal pouch: Forms middle ear structures and Eustachian tube — unrelated to thyroid.

• Rathke’s pouch: Forms anterior pituitary — not the thyroid.

• In Grave’s disease, thyroid follicles are hyperactive and show:

  • Tall columnar epithelium

  • Scalloped/irregular colloid due to increased uptake

  • Variable follicular sizes — some small, some enlarged, depending on activity

• Colloid amount is usually reduced, as hormone synthesis & release is very active.

Why the other options are incorrect:

• Large follicular size: Follicles are variable in size, not uniformly large.

• Acidophilic colloid: The colloid shows scalloping; no distinct acidophilic change typical.

• Large amount of colloid: In inactive thyroid — here, colloid is used up quickly → less colloid.

• Basophilic colloid: Colloid is not distinctly basophilic in hyperactive glands.

• Annular pancreas occurs when pancreatic tissue forms a ring around the duodenum → causing duodenal obstruction.

• Symptoms include:

  • Bilious vomiting (as obstruction is usually distal to the bile duct opening)

  • Feeding intolerance

  • Stomach dilation seen on imaging

• Common cause of neonatal duodenal obstruction.

Why the other options are incorrect:

• Pyloric stenosis:

  • Causes non-bilious vomiting (pylorus is proximal to bile entry).

  • Usually presents a few weeks after birth — not in first few days.

• Hyperplasia of pancreas:

  • Rare; would not typically cause duodenal obstruction.

• Hiatal hernia:

  • Affects esophageal hiatus — may cause reflux, not duodenal obstruction.

• Esophageal atresia:

  • Would cause drooling and non-bilious regurgitation, no duodenal obstruction or bilious vomiting.

• The exocrine pancreas secretes digestive enzymes (amylase, lipase, proteases).

• These enzymes are produced by serous acini — clusters of acinar cells.

• In pancreatitis, damaged acini leak large amounts of enzymes into the blood — leading to elevated serum amylase, lipase.

• Endocrine cells (alpha, beta, delta, islet cells) produce hormones — not digestive enzymes.

Why the other options are incorrect:

• Alpha cells: Secrete glucagon — endocrine.

• Beta cells: Secrete insulin — endocrine.

• Delta cells: Secrete somatostatin — endocrine.

• Islets of Langerhans: Clusters of endocrine cells — no digestive enzyme role.

• The first line of defense against hypoglycemia is glucagon, which rapidly increases blood glucose through glycogenolysis.

• Epinephrine acts as the second line of defense, stimulating:

  • Hepatic glycogenolysis

  • Gluconeogenesis

  • Inhibition of insulin release

  • Increased lipolysis

• Epinephrine helps maintain glucose availability when glucagon alone is insufficient.

Why the other options are incorrect:

• Growth hormone: Slower, long-term action — enhances lipolysis and reduces glucose uptake over hours.

• Insulin: Lowers blood glucose; would worsen hypoglycemia.

• Cortisol: Acts later (hours), supports gluconeogenesis — not an immediate defense.

• Glucagon: First line of defense, not second.

• Severely elevated triglycerides (> 1000 mg/dL) greatly increase risk of acute pancreatitis.

• This is due to excess chylomicrons impairing pancreatic blood flow and triggering inflammation.

• Patients often show xanthomas when triglycerides are elevated — seen here.

• Pancreatitis is the most immediate and life-threatening risk in this patient.

Why the other options are incorrect:

• Coronary heart disease: Elevated LDL is more strongly associated with CHD; triglycerides contribute less directly. While this is a long-term risk, pancreatitis is more urgent here.

• Cholelithiasis: Fibrates may increase gallstone risk, but no gallstone symptoms here; also, TG elevation more likely leads to pancreatitis first.

• Appendicitis: No relationship to triglyceride levels or lipid metabolism.

• Hepatitis: No mention of hepatotoxic drug use or liver enzyme abnormalities.

• The most common type of diabetic neuropathy is distal symmetric polyneuropathy (also called distal symmetric neuropathy).

• It typically presents with:

  • Bilateral symptoms starting in the feet (stocking pattern).

  • Burning, tingling, pins and needles sensations.

  • Loss of ankle jerks.

  • Mild weakness in distal muscles (toe dorsiflexion).

• It progresses slowly over months to years — fits this case perfectly.

Why the other options are incorrect:

• Amyotrophic neuropathy: Involves proximal muscle weakness and wasting, usually of thighs or pelvic girdle — not the distal, sensory-dominant pattern seen here.

• Entrapment neuropathy: Localized, single nerve compression (e.g., carpal tunnel); not symmetric stocking pattern.

• Mononeuropathy multiplex: Multiple single nerves affected in an asymmetric, patchy way — this patient has a symmetric pattern.

• Small fiber neuropathy: Presents mostly with pain and temperature sensory issues without weakness or reflex loss — here weakness and absent reflexes suggest involvement of large fibers too.

• Methimazole is an antithyroid drug used to treat hyperthyroidism by inhibiting thyroid hormone synthesis.

• One of its serious adverse effects is agranulocytosis (a marked reduction in neutrophils).

• Agranulocytosis presents with fever, sore throat, and low leukocyte count — exactly what this patient shows.

• Patients on methimazole are advised to report sore throat and fever promptly.

Why the other options are incorrect:

• Nadolol and Propranolol: Beta-blockers; used for symptomatic control in hyperthyroidism (reduce heart rate, tremors), but they do not cause agranulocytosis.

• Radioactive iodine: Destroys thyroid tissue, but agranulocytosis is not a typical side effect.

• Digoxin: Cardiac glycoside; used in heart failure and atrial fibrillation. Does not affect leukocyte count.

• Diabetes insipidus (DI) is a condition characterized by:

  • Excessive urination (polyuria)

  • Excessive thirst (polydipsia)

  • Very dilute urine

• The cause is a deficiency of ADH (also called vasopressin), or a lack of response to it.

  • Central DI → Low production of ADH

  • Nephrogenic DI → Kidneys do not respond to ADH

• ADH acts on the kidneys to promote water reabsorption. Without it, water is lost in urine.

Why the other options are incorrect:

• Angiotensin II: Involved in vasoconstriction and blood pressure regulation, not directly related to water reabsorption in DI.

• Aldosterone: Regulates sodium and water retention, but DI is specifically due to ADH issues.

• FSH: Follicle-stimulating hormone; unrelated to kidney water handling.

• Insulin: Regulates blood glucose; deficiency causes diabetes mellitus, not DI.

• The zona reticularis is the innermost layer of the adrenal cortex.

• It is responsible for producing weak androgens (e.g., DHEA, androstenedione).

• This layer is not fully developed during fetal life.

• It begins to develop postnatally, typically over the first few years after birth.

Why the other options are incorrect:

• In ninth month of fetal life: The fetal adrenal cortex at this stage is dominated by a large fetal zone and primitive cortical zones — not a developed zona reticularis.

• In fifth, sixth, or third month of fetal life:

  • Early adrenal development occurs, but zona reticularis formation does not occur this early.

  • The definitive cortex and zona fasciculata start forming during these months — zona reticularis comes later, after birth.

Pregnenolone is the first and most essential intermediate in the steroid hormone biosynthesis pathway. It is synthesized from cholesterol (27C) through the action of the enzyme desmolase (CYP11A1), located in the mitochondria of steroidogenic tissues (like adrenal cortex, ovaries, and testes).

Once formed, pregnenolone becomes the common precursor for all classes of steroid hormones, including:

• Glucocorticoids (e.g., cortisol)

• Mineralocorticoids (e.g., aldosterone)

• Androgens (e.g., testosterone, dihydrotestosterone)

• Estrogens (e.g., estradiol)

Thus, whether the end goal is estradiol or dihydrotestosterone (DHT), the pathway must begin with pregnenolone — making it the obligatory intermediate in all steroid hormone production.

❌ Why the Other Options Are Incorrect:

• Testosterone ❌
  Comes later in the pathway — it’s a precursor for DHT, but not required for estradiol, which can be formed from androstenedione.

• Androstenedione ❌
  Important downstream branch point, but pregnenolone must be formed first before reaching this stage.

• Dihydrotestosterone (DHT) ❌
  It’s a final product, not an intermediate. Made from testosterone via 5α-reductase.

• Progesterone ❌
  A downstream metabolite of pregnenolone via 3β-HSD, important in glucocorticoid and mineralocorticoid pathways, but not essential in the androgen/estrogen pathway.