Test: Disorders of Adrenal Cortex - NEET PG MCQ

The image depicts a patient suffering from Cushing syndrome, characterised by hypokalemic alkalosis resulting from the partial mineralocorticoid activity of cortisol.

The image depicts clitoromegaly and labial fusion in a virilised female child.

• The inguinal folds show no signs of mass or swelling.
• The primary cause is congenital adrenal hyperplasia.
• A deficiency in 21-hydroxylase, resulting from mutations or deletions of CYP21A, represents the most prevalent form of CAH, making up over 90% of cases.

Choice A: This is beneficial for assessing bone age, which is accelerated in CAH due to sex steroids.
Choice B: This is helpful for identifying CAH in female children with ambiguous genitalia.
Choice C: This is relevant due to salt loss and increased potassium levels resulting from reduced aldosterone production.
A 24-hour urinary chloride test is valuable in diagnosing renal tubular disorders such as Bartter syndrome and Gitelman syndrome.

Hyperkalemia is associated with a deficiency in mineralocorticoids. It has been observed that ACTH, through steroids, can inhibit the production of Interleukin-1. Conversely, in cases of glucocorticoid deficiency, IL-1 levels rise, which may reset the body's thermostat, resulting in fever as a symptom of glucocorticoid deficiency. This is often referred to as unexplained fever in medical literature. Postural hypotension is attributed to hyponatremia, which arises from the loss of feedback inhibition on AVP release due to glucocorticoid deficiency

• The appearance of 'lemon on sticks' is indicative of centripetal obesity.
• Weight gain contributes to insulin resistance, combined with the effects of cortisol, resulting in impaired glucose tolerance.

• Nelson's syndrome: Elevated ACTH levels (which exhibit partial MSH activity) following bilateral adrenalectomy.
• Addison's disease: Increased ACTH (which has partial MSH activity) due to adrenal cortex destruction and reduced cortisol.
• Hermansky-Pudlak syndrome: An autosomal recessive condition that leads to oculo-cutaneous albinism (reduced pigmentation) and bleeding issues caused by a platelet defect (platelet storage pool disorder).

The clinical manifestations of primary adrenal insufficiency are defined by the absence of both glucocorticoid and mineralocorticoid secretion. This leads to:

• Hypotension accompanied by hyponatremia.
• Hyperkalemia, which is attributed to low aldosterone levels.

In cases of secondary adrenal insufficiency, there is only a deficiency of glucocorticoids, as the adrenal glands remain intact and can still be regulated by the RAA system. It is important to note that adrenal androgen secretion is affected in both primary and secondary adrenal insufficiency.

Hyperpigmentation occurs in primary Addison's disease due to an excess of POMC-derived substances, while hypopigmentation is observed in secondary Addison's disease as a result of the depletion of these POMC derivatives.

The primary medical application of glucocorticoids for immunosuppression or in the management of inflammatory conditions is the leading cause of Cushing's syndrome. The most prevalent cause of ACTH-dependent Cushing syndrome is Cushing Disease, which arises from a pituitary adenoma. In contrast, the most frequent cause of ACTH-independent Cushing syndrome is adrenal adenoma.

The existence of hypertension and hypokalaemia indicates elevated aldosterone levels. For assessing primary hyperaldosteronism, the plasma renin/aldosterone ratio is beneficial.

• The ACTH stimulation test is performed for Addison's disease, which manifests with postural hypotension and hypokalaemia.
• A 24-hour urinary catecholamines test is utilised for diagnosing pheochromocytoma.
• Octreo-scan is employed to identify carcinoid tumours and primitive neuroectodermal tumours.

Metabolic alkalosis occurs in the presence of an excess of aldosterone, whereas options a, b, and c are associated with Addison's disease.

Beta Hydroxylase Deficiency is marked by:

• Excessive levels of 11-deoxycortisol, which can stimulate ENa, resulting in hypertension.
• Increased mineralocorticoids causing hypokalemia and metabolic alkalosis.
• Deficiency in glucocorticoids leading to hypoglycaemia, while excess ACTH contributes to hyperpigmentation in the genital area.
• Surplus adrenal androgens resulting in virilisation.

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Some individuals carrying polymorphisms in both CFTR genes exhibit few or no manifestations of cystic fibrosis until they reach adolescence or adulthood. At this point, they may show signs of:

• Pancreatitis
• Sinusitis
• Diffuse bronchiectasis
• Male infertility

In over 95% of males, the body and tail of the epididymis, the vas deferens, and the seminal vesicles are either obliterated or atretic. More than 95% of males are azoospermic due to the underdevelopment of Wolffian duct structures, although sexual function typically remains unaffected. The occurrence of inguinal hernia, hydrocele, and undescended testis is greater than anticipated.

• Hyponatraemia occurs due to glucocorticoid deficiency resulting from the loss of control over vasopressin inhibition.
• Clinical signs of secondary adrenal insufficiency include fatigue, hyponatraemia, and hypoglycaemia.

Sipple syndrome, also known as MEN 2A, is characterised by the presence of a pheochromocytoma. This condition is linked to:

• Weight loss
• Sympathomimetic activity
• Elevated levels of catecholamines

Most patients experience hypertension, typically mild, along with headaches. Malignant hypertension is uncommon. The hypertension arises from:

• Increased sodium reabsorption
• Expansion of extracellular volume

Signs of left ventricular hypertrophy (LVH) on ECG and chest X-ray are partly secondary to hypertension. However, the degree of LVH is disproportionate to the blood pressure levels when compared to those with essential hypertension. Patients with primary aldosteronism typically do not exhibit oedema, as they show an 'escape' phenomenon from the sodium-retaining effects of mineralocorticoids. Excessive aldosterone secretion enhances the renal distal tubular exchange of intratubular sodium for secreted potassium and hydrogen ions, leading to:

• Progressive depletion of body potassium
• Development of hypokalaemia

Potassium depletion is the cause of muscle weakness and fatigue, attributed to its impact on the muscle cell membrane. The polyuria observed results from impaired urinary concentrating ability (due to hypokalaemia) and is often accompanied by polydipsia. Metabolic alkalosis and increased serum bicarbonate levels stem from the loss of hydrogen ions in urine and their migration into potassium-depleted cells. This alkalosis is sustained by potassium deficiency, which enhances the proximal convoluted tubule's ability to reabsorb filtered bicarbonate.

Recommendations for pregnancies at risk include the administration of dexamethasone, a steroid that easily crosses the placenta, at a dosage of 20 µg/kg of pre-pregnancy maternal weight daily. This treatment inhibits the secretion of steroids by the fetal adrenal glands, including the release of adrenal androgens.

• If initiated by 6 weeks of gestation, it can diminish the virilisation of external genitalia in affected females.
• A chorionic villus biopsy is subsequently conducted to ascertain the sex and genotype of the fetus; treatment continues only if the fetus is a female at risk.
• DNA analysis of fetal cells obtained from maternal plasma for sex determination and CYP21 gene analysis may allow for earlier identification of the affected female fetus.

Ectopic site production accounts for 15%, whereas adrenal adenoma represents 10%, and the occurrence of adrenal carcinoma is at 1%. The causes of Cushing's Syndrome are as follows:
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Overall, the primary reason for Cushing's syndrome is the use of iatrogenic steroids. However, if the question pertains to an ACTH-dependent cause, the response should indicate a pituitary adenoma.

Cushing syndrome results in reduced glucose tolerance and elevated blood sugar levels.

• Most patients also encounter psychiatric issues, primarily manifesting as anxiety or depression.
• However, episodes of acute paranoid or depressive psychosis can also arise.

The presence of partial mineralocorticoid activity in cortisol accounts for hypertension and hypokalemia.

Weight gain accompanied by oligomenorrhea suggests Cushing syndrome.

• Cortisol inhibits the release of gonadotropins, which accounts for the amenorrhea.
• Hypertension observed in these individuals is a consequence of elevated cortisol, which also exhibits some mineralocorticoid effects.
• Excess glucocorticoids disrupt central regulatory mechanisms, resulting in the suppression of gonadotropins, leading to hypogonadism and amenorrhea.
• This interference also affects the hypothalamic-pituitary-thyroid axis, leading to reduced secretion of TSH (thyroid-stimulating hormone).

Weight gain associated with menorrhagia and isolated diastolic hypertension in this context would suggest thyroid dysfunction as the initial diagnosis
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Ectopic ACTH production is mainly triggered by hidden carcinoid tumours, most commonly found in the lung, but also in the thymus or pancreas. Approximately 25% of individuals with pulmonary carcinoid tumours do not show symptoms at the time of diagnosis. For those with symptoms, the most frequent clinical signs relate to bronchial obstruction, including:

• persistent cough
• hemoptysis
• recurrent or obstructive pneumonitis

Additional symptoms such as wheezing, chest pain, and dyspnoea may also be present. Although rare, various endocrine or neuroendocrine syndromes can be the initial clinical signs of either typical or atypical pulmonary carcinoid tumours. Ectopic ACTH production can also result from small cell lung cancer. Since the term small cell lung cancer is not included in the multiple-choice questions, it should be considered the second-best option.

Anasarca, or swelling, is not observed in CONN syndrome because of the salt escape mechanism.

• Despite the retention of salt and water due to excess aldosterone, the elevated preload will expand the right atrium, triggering the release of A.N.F.
• This rise in ANF will induce natriuresis, resulting in the loss of salt and water, counteracting the retention caused by aldosterone.
• This natriuresis, or loss of salt, will also be linked with water loss, resulting in polyuria.
• The consequent polyuria will lead to polydipsia.
• The observed weakness can be attributed to hypokalaemia.

Ectopic ACTH syndrome arises from the secretion of ACTH by bronchial carcinoid tumours, which occur in 2% of cases associated with MEN 1. The surplus of glucocorticoids surpasses the capacity of 11 beta-HSD₂ to swiftly convert cortisol into cortisone within the kidneys, leading to mineralocorticoid effects. These effects can present as:

• diastolic hypertension
• hypokalemia
• oedema

Due to atherosclerosis and hypertension, coronary events have been reported in these patients, as noted in Harrison.

Most prevalent form of CAH (21 hydroxylase deficiency) manifests as:

• hypoglycaemia
• hypotension
• virilisation

Administering hydrocortisone injections shortly after birth can assist in stabilising the infant by:

• raising blood sugar levels
• enhancing salt absorption in the kidneys

Methylprednisolone and dexamethasone exhibit minimal mineralocorticoid activity. Consequently, if the patient presents as hypovolaemic, hyponatraemic, or hyperkalaemic, higher doses of hydrocortisone are advisable due to its mineralocorticoid properties.

Two types of adrenal hyperplasia, namely 11-hydroxylase (CYP11B1) and 17-hydroxylase (CYP17) deficiency, lead to hypertension as a result of the build-up of supraphysiologic levels of deoxycorticosterone.

• This weak mineralocorticoid has minimal impact at physiological levels.
• However, it triggers sodium retention and hypertension when present in the supraphysiologic amounts associated with these conditions.

Primary hyperaldosteronism arises from either bilateral adrenal hyperplasia or an adrenal adenoma. Both of these conditions are independent and cause an overproduction of aldosterone. The negative feedback from the R.A.A.S system results in a reduction of renin production.

• Low renin hypertension is a characteristic of primary hyperaldosteronism.
• Factors contributing to low renin hypertension include:
  • Liddle syndrome
  • Conn's syndrome
  • Mineralocorticoid receptor mutation
  • Apparent mineralocorticoid excess (AME)
  • Glucocorticoid resistance
  • Gordon syndrome
  • Congenital adrenal hyperplasia (CAH)

• the absence of diurnal variation in plasma steroids
• and a positive overnight dexamethasone test.

In Addison's disease, the lack or reduced levels of aldosterone can result in:

• hypotension
• salt cravings
• hyperkalemia

Damage to the zona fasciculata may cause:

• hypoglycemia

While damage to the zona reticularis can lead to:

• loss of axillary and pubic hair

Hypokalemia is observed in Conn syndrome.

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Maternal virilizing tumour

• Causes masculinization of a female fetus.
• Thus, the findings would be ambiguous genitalia with female internal genitalia including uterus (Mullerian structures) and no testis (no inguinal masses as seen in AIS).
• The BP and pigmentation would not be affected

AIS (Androgen Insensitivity Syndrome)

• In this case, the androgen receptors do not respond to the androgens.
• Hence, there will be feminization of a masculine fetus.
• There is normal breast development, short vagina and absence of uterus (since the person is a male)
• Testis usually does not descend completely (cryptorch idism) and present as masses in the inguinal region.

Congenital Adrenal Hyperplasia

• This is due to deficient steroidogenesis.
• In 17-a and 11-P enzyme deficiencies, there is mineralocor- ticoid excess leading to hypertension
• In 21 -a deficiency, adrenal hyperplasia with normotension, ambiguous genitalia with clitoris enlargement and labial fusion, and hyperpigmentation are the presenting features.

5-a-reductase deficiency

• This condition occurs in males.
• Hence, there is ambiguous genitalia and male internal genitalia (testis in the normal position and absence of Mullerian structures).

In Conn's syndrome, there is a functioning salt escape mechanism that results in the lack of pedal oedema. The rationale is that although aldosterone levels are significantly elevated in Conn's, which should typically lead to salt and water retention and the formation of oedema, the increase in volume causes the right side of the heart to dilate. This dilation triggers the release of A.N.P (Atrial Natri-Ureteric Peptide).

• This substance induces the loss of water.
• It counteracts the retention caused by aldosterone.

Cushing syndrome is characterised by elevated cortisol that demonstrates partial aldosterone activity. As a result, the heightened aldosterone levels account for hypertension and potassium deficiency. Liddle's syndrome, also referred to as Pseudoaldosteronism, is an autosomal dominant condition marked by the misregulation of an epithelial sodium channel (ENaC) owing to a genetic mutation at the 16p13-p12 locus. This leads to:

• Excessive sodium reabsorption
• Potassium loss from the renal tubule

It is managed through a combination of a low sodium diet and potassium-sparing diuretic medications (e.g., amiloride). In cases of hyperaldosteronism, the elevated aldosterone levels promote increased sodium and water retention, resulting in hypertension. Concurrently, potassium loss at the ENaC receptor due to aldosterone's effect accounts for hypokalemia. For patients with end-stage renal disease (ESRD), the rise in renin contributes to hypertension, while kidney damage reduces potassium excretion, leading to hyperkalemia.