Pheochromocytoma Notes

Parathyroid, Adrenals And Pituitary Glands Parathyroid Glands Surgical Anatomy

• They are the endocrinal glands situated in the neck which secrete the hormone parathormone (PTH). Their secretion is not dependent on the pituitary gland.
• They are 4 in number; 2 on the right, and 2 on the left. It is pinkish in children, and yellow to brown in adults.

Read And Learn More: Clinical Medicine And Surgery Notes

• Superior parathyroids are derived from the endoderm of the 4th branchial arch and thus, they are developed with the thyroid gland.
• Superior parathyroids are found in relation to the inferior thyroid artery in the middle of the posterior aspect of the thyroid gland. They are constant in position. They are smaller (20–40 mg).
• Inferior parathyroids develop from the endoderm of 3rd branchial arch (with thymus) and are not constant in position.
  • They may be seen in the lower pole, within the fascial sheath of the thyroid gland low down in the neck (rarely in the mediastinum), outside the fascial sheath or even within the thyroid gland. They are large (30 to 50 mg).

Blood Supply

• The inferior thyroid artery supplies both the parathyroids in about 95% of cases by a leash of vessels. Ligature of both thyroid arteries may not result in hypoparathyroidism because there is adequate collateral circulation.

Histology

• Principal cells are the cells which secrete PTH (parathormone). Water-clear cells are found in hyperplastic and neoplastic glands.

Congenital Anomaly And Syndrome DiGeorge’s Syndrome

• Congenital absence of the parathyroid glands and thymus. Neonatal hypoparathyroidism + absence of thymus-dependent lymphoid system.

Physiology—Action Of Pth

1. Resorption and mobilization of calcium from the bone.
2. Increased reabsorption of calcium from the kidney and prompting excretion of phosphate.
3. Enhances absorption of calcium from the gut.
   • Thus, PTH increases serum calcium levels.
   • Normal serum calcium level 9–11 mg/100 ml (total).
   • In normal persons, the PTH is balanced by calcitonin, secreted from C cells of the thyroid glands.

Tetany

Tetany is a condition wherein there is hyperexcitability of peripheral nerves.

Tetany Causes of Tetany

1. Hypoparathyroidism: It results from the surgical removal of parathyroids. Subtotal thyroidectomy and near-total thyroidectomy are the most common causes of tetany. After thyroidectomy, it may be temporary or permanent (if all 4 parathyroids are removed or deprived of their blood supply). The incidence is around 1–2%.
2. Severe respiratory alkalosis can cause tetany as in hyperventilation.
3. The low calcium levels can occur due to dietary factors, due to poor absorption from the gut acute pancreatitis, or chronic renal failure.
4. Osteomalacia and rickets due to deficiency of vitamin D.
5. Hypokalaemic alkalosis of pyloric stenosis.

Tetany Signs and Symptoms

1. Tingling and numbness of the fingers, toes, and lips (circumoral paraesthesia), at times with circumoral pallor.
2. Cramps of the hands and feet.
3. In severe hypocalcemia, there may be carpal spasms. Metacarpophalangeal (MP) joints are flexed, extension at interphalangeal joints, adduction of the thumb, thumb in palm deformity (obstetrician’s hand). In the foot, extension in the ankle joints and flexion of the toes may be seen.
4. Stridor is a dangerous complication of severe tetany due to spasms of muscles of respiration.
5. Latent tetany can be diagnosed as follows:
6. Tap the facial nerve at the angle of the jaw. This produces twitching of eyelids, corner of the mouth, etc. It is called the Chvostek sign. It indicates facial nerve hyperexcitability.
7. Trousseau’s sign: When a blood pressure cuff is applied to the arm and is inflated above the systolic pressure (200 mmHg), the hand goes into spasm (obstetrician’s hand).
8. Spasm of intraocular muscles results in blurring of vision.
9. Convulsions, even though rare, can occur in infants.

Features Of Tetany

• Circumoral paraesthesia
• Carpopedal spasm
• Chovstek’s sign
• Trousseau’s sign

Tetany Diagnosis

This is established by estimating serum calcium level which is usually < 7 mg%.

Tetany Treatment

1. Oral calcium such as calcium lactate, and calcium gluconate may relieve mild symptoms.
2. In acute cases, injection of calcium gluconate 10% (10 ml) should be given slowly
   intravenously over 10 minutes to avoid cardiac arrhythmias.
3. If any precipitating cause is detected, it needs to be corrected.

Hyperparathyroidism

Hyperparathyroidism is an uncommon disease and occurs due to an increased activity of parathyroids and manifests as hypercalcemia.

Hyperparathyroidism Causes

1. Single chief cell adenoma is the most common cause (80%).
2. It can be due to diffuse hyperplasia involving all 4 glands (5 — 10% of cases)
3. Very rarely it can be due to carcinoma arising in the parathyroid glands.

Hyperparathyroidism Pathology

• Adenoma—Reddish brown—Only 1 gland is enlarged
• Chief cell hyperplasia—Reddish brown— > 1 gland is enlarged
• Water cell hyperplasia—Chocolate brown— > 1 gland is enlarged
• Adenoma can be a part of multiple endocrine neoplasia (MEN) syndrome

Hyperparathyroidism Pathology Clinical features

• Common in females, the female/male ratio is 2:1.
• Age: 20–60 years, the most common age group is 5th decade.
• Incidence is 1:1000 patients
• The most common presentation is asymptomatic hypercalcaemia in about 50% of the patients and renal stones in 25% of the patients. The clinical features are as follows:

1. Bone disease

• Due to increasing levels of PTH, extensive skeletal decalcification occurs.
• This results in bony pains, pathological fractures due to brittle bones, subperiosteal erosions, cysts in the phalanges, jaw bone (mandible), skull, etc.
• They are called pseudotumors. The changes are similar to those seen in osteitis fibrosa cystica (von Recklinghausen’s disease).

2. Renal disease

• Increased calcium levels result from increased calcium absorption from the kidneys. Hence, patients are prone to developing renal stones and nephrocalcinosis (calcification of the kidney), renal ischaemia and hypertension.
• Calcium also increases the tone of the vessels which adds to the hypertension. Primary hyperparathyroidism is the cause of stones in 1–3% of all patients with kidney stones and in 10 per cent of those who have a recurrence of stones.

Adrenal Glands

• Adrenal glands are the important endocrinal glands which are essential for life. Life-saving hormones such as corticosteroids and catecholamines are secreted by the adrenals.
• The disorders of the adrenal cortex include Addison’s disease, Cushing’s syndrome, Conn’s syndrome, etc.
• These are of great interest to the physicians. Tumours arising from adrenal medulla including neuroblastoma and phaeochromocytoma are of interest to surgeons.

Classification of Tumours of Adrenal Medulla

1. Neoplasm of the sympathetic neurons

1. Ganglioneuroma: It is a benign neuronal tumour, that commonly arises from the retroperitoneal lumbar sympathetic trunk. FNAC, ultrasound followed by surgical excision is the management.
2. Neuroblastoma

2. Neoplasm of the chromaffin cells

• Phaeochromocytoma

Neuroblastoma

• It occurs in 1 in 10,000 live births.
• It is the most common solid tumour in infancy and childhood.
• It originates from the neural crest. Hence, it can be found from orbit to the pelvis where sympathetic nerve tissue is found.
• The adrenal gland is the most common site of neuroblastoma.
• As the name suggests, the tumour occurs due to malignant proliferation of the neuroblasts or failure of maturation of primitive sympathetic nerve cells, the neuroblasts.

Neuroblastoma Clinical Features

• 50% of children present to the hospital under the age of one year and 80–90% are less than 3 years of age.
• An abdominal mass is the most common presenting feature. The mass has all the features of a renal mass but the location is slightly higher. It is firm to hard, nodular and fixed. The child is sick with weight loss, fever, abdominal distension, anaemia, etc.
• Functional tumours produce diarrhoea and hypokalaemia due to the release of vasoactive intestinal polypeptide (VIP), sweating and flushing due to the release of catecholamines.
• Proptosis and periorbital swellings are due to bony metastasis and subcutaneous nodules are quite common.
• Posterior mediastinal neuroblastomas can produce cord compression and even paraplegia due to protrusion within the spinal canal (dumbbell tumours).

Neuroblastoma

• The most common solid tumour in infancy and childhood.
• Adrenals is the most common site
• Mass abdomen and metastasis are common presenting features
• Surgical excision is the best treatment
• The younger the child, the better the prognosis
• Highest incidence of spontaneous remission

Types Of Neuroblastoma

1. Pepper type: Right-sided tumours with secondaries in the liver.
2. Hutchinson’s type: Left-sided tumour with metastasis in bones—Orbit and skull.

Neuroblastoma Investigations

1. Vanillyl mandelic acid (VMA) and homovanillic acid (HVA) are the byproducts of catecholamines passed in the urine. 24-hour urinary excretion of catecholamines and these 2 metabolites will be very high.
2. A plain X-ray abdomen shows fine stippled calcification. X-ray chest to rule out cannon-ball secondaries.
3. Abdominal ultrasound and computed tomography (CT) can define the mass, nature and extent and can detect hepatic metastasis.
4. Excretory pyelography is done to rule out renal mass. Displacement of the kidney, laterally and downwards, is also a feature.
5. Magnetic resonance imaging (MRI) is better than a CT scan in detecting the mass as well as bony metastasis.
6. Bone marrow aspiration is positive in around 60–70% of cases.

Neuroblastoma Treatment

• Early cases respond very well to surgical excision.
• However, many children present with metastasis and, chemotherapy and radiotherapy is given first to control the disease followed by surgical excision. Autologous bone marrow transplantation has improved the outlook for patients with advanced disease.

Phaeochromocytoma

• As the name suggests, phaeochromocytoma is a neoplasm arising from chromaffin cells.
• 90% of the tumour occurs in adrenals
• Extra-adrenal sites include the organ of Zuckerkandl (the most common site), urinary bladder, renal hilum, chest, neck, etc. These are the sites of the paraganglionic system. In about 5% of cases, the tumour can be a component of multiple endocrine neoplasia (MEN)
• Type Ha or Type lib.
• Another syndrome associated with Phaeochromocytoma is von Hippel-Lindau syndrome.
• The clinical manifestations are due to the release of adrenaline and noradrenaline.
• When the level of noradrenaline is high, symptoms are severe.

Phaeochromocytoma Pathology

• It is a soft, highly vascular tumour consisting of large sympathetic ganglionic cells. Most of the cells are differentiated.
• Usually, it is small in size and well-encapsulated.
• Sometimes, it can present as a large abdominal mass.
• Microscopic features are polygonal or spheroidal chromaffin cells within a vascularised fibrous stroma.

Phaeochromocytoma

• 10% Bilateral
• 10% Malignant
• 10% Extra-adrenal
• 10% Multiple
• 10% Familial
• 10% Children

Other Neuroectodermal Anomalies With Phaeochromocytoma

• Neurofibromatosis
• Acoustic neuromas
• Meningioma
• Glioma
• Astrocytoma

Phaeochromocytoma Clinical features

• The most common presenting feature is paroxysmal or persistent hypertension. It is associated with palpitation, fever, pallor, tremors, sweating and severe headache.
• The paroxysmal attack may last for a few minutes to a few hours.
• The factors which stimulate an attack are:
  • Surgery
  • Invasive procedure
  • Late pregnancy
  • Drugs—Histamine, glucagon, etc.
  • Palpation of the mass.

Hypertension In Phaeochromocytoma

• Paroxysmal
• Persistent
• Palpitations
• Pallor
• Profuse sweating
• Pain abdomen
• Palpation of the mass

A high index of suspicion is necessary to diagnose phaeochromocytoma in a hypertensive patient.

Phaeochromocytoma Investigations

1. Urinary levels of free catecholamines, vanillylmandelic acid (VMA) in excess of 7 mg/24 hours and meta-adrenaline 1–3 mg/24 hours are suggestive of phaeochromocytoma.
2. Computed tomography:
   • Noninvasive, safe investigation
   • It has a high degree of accuracy
   • It can pick up lesions of less than 1 cm in size
3. ¹³¹I-Metaiodobenzylguanidine (MIBG) scan
   • Iodine labelled MIBG (radionuclide) scan is found to be very specific for
     phaeochromocytoma.
   • This radionuclide scan locates only abnormal adrenal tissue and is more useful in detecting ectopic sites of phaeochromocytoma.

Phaeochromocytoma Treatment

• Surgical removal is the treatment. However, good pre-operative preparation is essential before doing surgery. It includes control of blood pressure and tachycardia, by a and β- blockers.
• Contraction of vascular bed which occurs due to catecholamines results in hypovolaemia which is to be corrected by IV fluids.

Phaeochromocytoma (Preoperative Preparation)

• Phenoxybenzamine 20–60 mg/day for 3–4 weeks before surgery to control hypertension.
• Propranolol 20–60 mg/day for 5–7 days before surgery to control tachycardia and arrhythmias.
• Plenty of fluids before surgery to correct hypovolaemia.

• First, an alpha-adrenergic blocker such as phenoxybenzamine is given to control hypertension and to permit the re-expansion of intravascular volume. Only after the complete alphaadrenergic blockade, beta-adrenergic blockade may be added.

Phaeochromocytoma Surgery

Excision is the treatment. Certain steps of excision (adrenalectomy) are as follows:

• Sodium nitroprusside is to be kept ready to treat hypertension on the table as it is a direct peripheral vasodilator (0.5 to 10 µg/kg/minute).
• Thorough search in the abdomen for other sites, due to the possibility of multiple tumours
• Postoperative hypotension can be a serious problem which needs to be treated with large volumes of plasma expanders, blood transfusions, corticosteroids and vasopressors.

Precautions During Surgery

• Midline incision for familial cases
• Anterior or posterior approach for sporadic cases
• Careful positioning
• Gentle handling
• Haemodynamic monitoring
• Ligation of adrenal vein first
• Avoid rupture of the tumour to prevent recurrence
• Laparoscopic adrenalectomy is very popular now

Incidentalomas

• Incidentally detected adrenal masses
• Detected by ultrasound or CT scan
• The majority of such tumours are non-functioning cortical adenomas of no clinical significance

Pituitary Glands

• It is the endocrinal gland situated in the cavity of the pituitary fossa—sella turcica of the sphenoid bone.
• The shape of the cavity containing the pituitary gland mimics a Turkish horse saddle (Sella Tursica).
• The gland is located at the centre of the head at the junction between the cranial cavity and nasal cavity.
• It is often called Master Gland because it controls and regulates other endocrine glands.
• On each side, the dura separates the pituitary from the cavernous sinus. Optic chiasma is at a higher level—pituitary rumours (when they extend above) can press on the medial side of the optic nerves.

Pituitary Glands Anatomy

It has two parts histologically very different from each other anterior lobe (anterior pituitary) and posterior lobe (posterior pituitary).

1. Anterior lobe: The larger anterior part is called as anterior lobe, also called adenohypophysis.
   • It is very vascular and cellular. Hence, it is the site of the production of some important hormones.
   • The anterior lobe is formed from Rathke’s pouch (ectodermal).
2. Pars intermedia is that portion of the anterior lobe through which the anterior lobe is connected to the posterior lobe. It is a narrow zone of gland substance.
3. Posterior lobe: The smaller posterior lobe (also called neurohypophysis) is less vascular and more of fibrous tissue. Hence, less active. The posterior lobe is connected with the stalk downwards and forwards from the tuber cinereum. It develops as a diverticulum from the floor of the diencephalons (neuroectoderm).
4. Microscopic anatomy: The anterior lobe has 3 kinds of cells. About 50% of cells are chromophobe cells which have pale agranular cytoplasm. The remaining cells are eosinophilic or basophilic cells. Eosinophil cells are much more than basophils.
5. Blood supply: The posterior lobe and the stalk are supplied by branches of the internal carotid artery. The anterior lobe is supplied by the capillaries from the above blood supply. Veins drain into the intercavernous anastomosis.

Pituitary Glands Physiology

Hormones secreted by the anterior pituitary

1. GH (growth hormone) or somatotropin. Its action is on the growth of the body. Indirectly it acts on the liver.
   • The liver secretes somatomedin C or insulin-like growth factor which helps in chondrogenesis, skeletal growth, increased protein synthesis and cell proliferation.
   • Hypersecretion of this hormone before puberty gives rise to gigantism and after puberty acromegaly. Decreased growth hormone secretion in childhood causes Dwarfism.
2. ACTH: Adrenocorticotrophic hormone is for the adrenal cortex.
   • Complete stoppage of ACTH production is fatal causing a so-called Addisonian crisis if medical treatments with replacement steroids are not instituted immediately
   • Addisonian crisis is a condition of shock related to the lack of corticosteroids in the body.
3. TSH (Thyroid-stimulating hormone): Thyroid hormones generally have a role in maintaining metabolic homeostasis and have a counterbalancing effect on the production of TSH in the pituitary gland (negative feedback).
4. Follicular stimulating hormone (FSH) and Luteinising hormone (LH): These two hormones are known as gonadotropic hormones.
   • LH and FSH control the production of female sex hormones such as estrogen and progesterone as well as the production of testosterone.
   • These sex hormones generally function to produce sexual characteristics and the reproductive cycle and also have counterbalance effects to the pituitary gland (negative feedback).
5. Prolactin: Increased secretion of prolactin causes galactorrhoea. Prolactin is a hormone active in milk production.
   • Prolactin secretion is high in a woman during lactation for a newborn baby.
   • Overproduction of prolactin can result in aberrant milk production (even in males) and significantly decreased libido.
   • Dopamine produced in the brain is the natural negative regulator of prolactin production, and therefore, dopaminergic agonists (such as bromocriptine) are used as a medical treatment for the overproduction of prolactin.

Hormones secreted by the posterior pituitary

These hormones are synthesized in the neurons of the hypothalamus, supraoptic and paraventricular nuclei.

1. ADH: Antidiuretic hormone (vasopressin). It decreases the volume of water lost in the urine, thus helping to maintain body water content. Diabetes insipidus occurs due to a deficiency of ADH.
2. Oxytocin: It acts on the myoepithelial cells of the breasts and causes the ejection of milk from the alveolar ducts of the breast. It also causes severe contraction of the myometrium, which helps in the delivery of the foetus.