Test: Parathyroid and Adrenal Glands - 1 - NEET PG MCQ

Secondary hyperparathyroidism (Secondary HPT) often arises in cases of chronic renal failure. It may also occur in hypocalcemia resulting from insufficient calcium or vitamin D intake, or from malabsorption.

The pathophysiology of HPT in chronic renal failure is associated with:

• Hyperphosphatemia leading to hypocalcemia
• Deficiency of 1,25-dihydroxy vitamin D due to renal tissue loss
• Low calcium intake
• Reduced calcium absorption
• Abnormal parathyroid cell responses to extracellular calcium or vitamin D in both in vitro and in vivo settings

Clinical features typically include patients being hypocalcemic or normocalcemic.

Treatment usually involves:

• A low-phosphate diet
• Phosphate binders
• Ensuring adequate intake of calcium and 1,25-dihydroxy vitamin D
• A high calcium, low-aluminium dialysis bath

If PTH levels remain elevated despite optimal treatment, parathyroidectomy should be considered.

Tertiary hyperparathyroidism is characterised by autonomous parathyroid gland function and can lead to issues similar to primary hyperparathyroidism (PHPT), including:

• Pathologic fractures
• Bone pain
• Renal stones
• Peptic ulcer disease
• Pancreatitis
• Mental status changes

Operative intervention is warranted in cases of:

• Symptomatic disease
• Persistent autonomous PTH secretion for more than one year following a successful transplant

Treatment options include subtotal or total parathyroidectomy with autotransplantation, along with upper thymectomy.

Approximately 85% of the parathyroid glands are located within 1 cm of the junction between the inferior thyroid artery and the recurrent laryngeal nerves (RLNs).

To expose a “suspicious” fat lobule, the thin fascia covering it should be incised with a sharp curved hemostat and scalpel. This technique frequently causes the parathyroid gland to “pop” out.

Alternatively, performing gentle, blunt dissection with a peanut sponge between the carotid sheath and the thyroid gland often uncovers a “float” sign, indicating the position of the abnormal parathyroid gland.

• Normal parathyroids exhibit a light beige colour, appearing only slightly darker or brown compared to the surrounding fat.
• Most common locations for ectopic parathyroid glands are:
  • Paraesophageal
  • Mediastinal
  • Intrathymic

Individuals receiving surgical intervention for endogenous hypercortisolism need glucocorticoid replacement. Steroids are not administered before the operation as these patients are already experiencing hypercortisolemia. Instead, hydrocortisone 100 mg is provided intravenously following the excision of the second hyperplastic adrenal gland.

The cluster of symptoms indicates a possibility of MEN-2A (Sipple syndrome), thus the patient ought to be evaluated for pheochromocytoma through the measurement of:

• Urinary metanephrines
• Vanillylmandelic acid (VMA)
• Catecholamines

Conditions associated with MEN-2A (Sipple syndrome) include:

• Medullary carcinoma of the thyroid
• Hirschsprung’s disease
• Pheochromocytoma
• Cutaneous lichen amyloidosis
• Parathyroid hyperplasia or adenoma

Syndromes linked to Pheochromocytoma include:

• Multiple Endocrine Neoplasia Type 2A (MEN-2A)
• Multiple Endocrine Neoplasia Type 2B (MEN-2B)
• Von Hippel-Lindau (VHL) syndrome
• Neurofibromatosis Type 1 (Von Recklinghausen syndrome)
• Sturge-Weber syndrome

The primary reason for adrenal insufficiency, specifically Addison's disease, in developing nations is Tuberculosis, which is then followed by autoimmune conditions.

Incidentaloma refers to adrenal masses that are discovered incidentally through imaging conducted for other, non-adrenal conditions. The differential diagnosis encompasses both secreting and non-secreting neoplasms. For patients with a history of cancer, metastatic disease is the most probable cause of adrenal masses, especially when they are bilateral. In individuals without a known history of malignancy, more than 80% of incidentalomas are likely to be non-functioning cortical adenomas or other benign lesions that do not necessitate surgical intervention.

Clinical Evaluation involves a diagnostic work-up for incidentalomas aimed at identifying patients who may benefit from adrenalectomy. This process integrates hormonal assessment with size criteria:

• The evaluation starts with a detailed history, focusing on prior malignancy, hypertension, and symptoms linked to glucocorticoid or sex steroid excess.
• Biochemical tests for hormonally active tumours are conducted, followed by an assessment of size criteria.
• Tumours larger than 6 cm present over a 25% risk for malignancy.
• CT-guided FNAC is seldom useful in evaluating adrenal masses and can pose risks.
• The diagnosis of primary adrenal malignancy cannot be reliably determined based solely on cytological criteria.
• FNAC is typically reserved for patients with a history of extra-adrenal malignancy where the clinician aims to confirm metastatic disease.
• Pheochromocytoma must be ruled out before proceeding with such a procedure to prevent triggering a potentially fatal hypertensive crisis.

Management of Adrenal Incidentaloma involves surgical intervention for hormonally active tumours and masses with a significant risk of malignancy. Most incidentalomas can be excised laparoscopically, apart from those that exhibit clear malignant characteristics on imaging:

• All incidentalomas measuring over 5 cm should be removed, while those between 3–5 cm should be strongly considered for removal.
• For tumours smaller than 3 cm, follow-up with CT every 6 months is advised.

Indications for surgery in incidentalomas measuring 3–5 cm include:

• Suspicious imaging features (such as heterogeneity, high attenuation, or irregular borders).
• Younger age.
• Minimal surgical risk factors.
• Growth of the tumour over time.
• Patient preference.

Adrenocortical carcinoma is an uncommon tumour. Over half of these carcinomas are functional, with Cushing’s syndrome being the most frequently observed, followed by virilisation.

Pathology

• Microscopically, the tumour presents hyperchromatic cells with large nuclei and prominent nucleoli.
• It is quite challenging to differentiate between benign adrenal adenomas and carcinomas based solely on histological examination.
• Capsular or vascular invasion is the most dependable indicator of malignancy.

Clinical Features

• Nearly all cases occur in individuals aged 40 to 50.
• There is no gender preference.
• More than half of adrenocortical carcinomas are functional, with Cushing’s syndrome being the most prevalent, followed by virilisation.
• Tumours are typically very large at initial diagnosis (mean size of 9 to 12 cm).
• Metastases may occur in the lymph nodes, liver, and lungs.

Diagnosis

• CT scans reveal a heterogeneous mass with irregular or indistinct borders, central necrosis, and invasion into surrounding tissues.
• The size of the adrenal mass is the most critical factor in diagnosing malignancy.

Treatment

• Radical open surgery involves en-bloc resection of adjacent organs or regional lymphadenectomy, or both.
• Ketoconazole, aminoglutethimide, or metyrapone (KAM) are used to manage steroid hypersecretion.
• Mitotane is the main chemotherapeutic agent, derived from the insecticide DDT, though its use is restricted due to significant gastrointestinal and neurological side effects.

Prognosis

• The most crucial predictor of survival is the adequacy of the surgical resection.
• The prognosis is poor, with a 5-year survival rate of 15 to 20%.
• Patients who undergo incomplete resection have a very limited life expectancy, with a median survival of less than 1 year.
• There is a high tendency for local recurrence and metastases, typically within 2 years.

Conn’s Syndrome (Primary Hyperaldosteronism) can present with the following clinical laboratory findings:

• Muscle weakness and fatigue (resulting from hypokalemia)
• Hypertension without accompanying oedema
• Polyuria and polydipsia
• Hypokalemia
• Metabolic alkalosis
• Hypernatremia
• Increased aldosterone levels
• Low renin levels

Adrenal adenomas observed on contrast-enhanced CT or MRI exhibit a quicker uptake and a comparatively faster washout of contrast material than non-adenomas. CT characteristics of adrenal adenomas include:

• Clearly defined or sharply demarcated, measuring less than 5 cm in size
• Low attenuation (<10 hu)attributed to lipid>
• Mild, homogeneous enhancement
• Relatively swift washout of contrast material, due to the absence of large interstitial spaces

A rapid washout is a notable feature of adenomas.

Pheochromocytoma tumours originate from chromaffin cells located in the adrenal medulla and other areas.

• The peak occurrence is in the 4th and 5th decades of life, with no specific gender preference.
• The most common site for extra-adrenal tumours is the organ of Zuckerkandl.

Often referred to as the 10% tumour due to the following characteristics:

• 10% are bilateral
• 10% are malignant
• 10% occur in paediatric patients
• 10% are extra-adrenal
• 10% are familial

Etiology and risk factors include:

• Can be either familial or sporadic.
• Familial cases may be syndromic or non-syndromic.
• Syndromes associated with pheochromocytoma include:
• MEN-2A and MEN-2B
• Von Recklinghausen syndrome
• VHL syndrome
• Sturge-Weber syndrome
• Non-syndromic familial pheochromocytomas are most frequently linked to mutations in succinyl dehydrogenase D and B.

Pathology reveals:

• Most tumours are unilateral and solitary.
• When pheochromocytoma arises in MEN syndrome, they are seldom malignant.
• Conversely, individuals with germline SDHB mutations tend to exhibit a higher likelihood of extra-adrenal and malignant tumours.
• Tumours lack innervation, meaning catecholamines are not produced from neural stimulation.
• Tumours also release endogenous opioids, adrenomedullin, erythropoietin, PTHrP, neuropeptide Y, and chromogranin A.
• Most pheochromocytomas produce both NA and Adr, with NA being greater than Adr.
• Extra-adrenal pheochromocytomas exclusively secrete NA due to a deficiency of the enzyme PNMT (Phenylethanolamine-N-Methyltransferase).
• Pheochromocytomas associated with MEN secrete Adr alone.
• Increased levels of dopamine and homovanillic acid are typically observed in malignant lesions.

Histologically, the tumour comprises:

• Polygonal to spindle-shaped chromaffin cells arranged in small nests or alveoli (Zellballen) within a rich vascular network.
• Nuclei are round with a salt-and-pepper chromatin appearance.
• Criteria for malignancy are determined solely by the presence of metastases, as capsular or vascular invasion can occur in benign tumours.

Clinical features include a classic triad:

• Headache
• Diaphoresis
• Palpitations

Nelson’s syndrome can develop when adrenalectomy is performed in the presence of residual corticotroph adenoma tissue, leading to:

• Rapid enlargement of the pituitary tumour
• Increased pigmentation due to elevated ACTH levels

Radiation therapy may be necessary to prevent the onset of Nelson’s syndrome following adrenalectomy.

In cases of primary adrenal Cushing’s syndrome, adrenalectomy may result in loss of negative feedback to the pituitary, potentially leading to the formation of a pituitary adenoma and subsequent Nelson’s syndrome.

The embryonic development of the kidneys and adrenal glands differs; therefore, even in cases of renal agenesis, the adrenal glands will remain in their normal location.

• Headache is a common symptom of MC.
• Hypertension is a manifestation of MC (note that hypertension is not classified as a symptom).
• Weight loss occurs due to heightened energy expenditure.
• Cardiac issues may include:
  • Sinus tachycardia,
  • Sinus bradycardia,
  • Supraventricular arrhythmia, and
  • Ventricular premature contractions.
• Carbohydrate intolerance and elevated haematocrit (indicating volume depletion) may also be present.

Diagnosis can be made through:

• Biochemical tests: The most sensitive screening test is urinary catecholamines and VMA levels.
• The best diagnostic test is fractionated plasma metanephrines.

For pharmacological testing:

• A positive response to phentolamine is indicated by a reduction in BP of at least 35/25 mm Hg after 2 minutes; however, this is not diagnostic and requires biochemical confirmation.
• Glucagon infusion can increase catecholamine release, resulting in episodes of hypertension.

In terms of imaging:

• MRI is the investigation of choice (IOC) for adrenal and extra-adrenal pheochromocytoma, as well as in pregnancy, with a sensitivity of 95% and specificity of 100% for pheochromocytoma.
• CT scans should be conducted without contrast to prevent hypertensive crises.
• A MIBG scan is beneficial for extra-adrenal pheochromocytoma, but MRI remains the IOC even in these cases.
• Biopsies are contraindicated as they can trigger hypertensive crises.

Treatment involves:

• Adrenalectomy, which is the treatment of choice (TOC).
• Laparoscopic adrenalectomy is preferred for tumours smaller than 5 cm.
• Preoperatively, alpha-blockers (such as phenoxybenzamine) should be administered.
• Beta-blockers are only indicated if tachycardia occurs and should not be given until the patient is fully alpha-blocked to prevent hypertensive crises due to unopposed alpha stimulation.

According to Schwartz, 9th edition, page 1399, recent studies have indicated that plasma metanephrines are the most reliable tests for detecting pheochromocytomas, with sensitivity nearing 100%.