Adrenals & Parathyroid

Done by: Zaid Al-Ghananeem

Embryology

-Endodermal origin

-Superior parathyroid glands are derived from the 4th pharyngeal pouch.

-Inferior parathyroid glands are derived from the 3rd pharyngeal pouch.

-Long descent pathway; thus there is an increased incidence of an ectopic gland:

1) If undescended: cranial to the super lobe of thyroid

2) Excessive descent: mediastinum (1% of population)

3) Other sites: thymus is the most common ectopic site.

Anatomy and physiology

-Number of glands:85% of the population has 4 glands.5% of the population has 5 glands. 10% of the population has 3 glands.

Site:postero-lateral aspect of the thyroid gland.

Blood supply in 80% of the population : inferior thyroid artery

The superior parathyroid glands are located near the junction of the inferior thyroid artery and recurrent laryngeal nerve, usually superior to the artery and posterior to the nerve.

The inferior parathyroid glands are located anterior to the recurrent laryngeal nerve at the lower pole of the thyroid lobe.

Histology

-The parathyroid gland has a thin fibrous capsule, and contains cells : chief cells (predominant) and oxyphil cells.

-Chief cell secretes PTH which regulates calcium levels through 3 main organs :

1-Small Intestine : Increase ca absorption (ca is absorbed from duodenum and proximal jejunum.

2-Kidney: stimulates calcium reabsorption, inhibits phosphate reabsorption and stimulates the synthesis of vitamin D.

3-Bone: stimulates releasing of calcium and phosphate by increasing osteoclast activity.

-Bone is the largest calcium reservoir in the body.

-The total serum calcium levels range from 8.5 to 10.5 mg/dL (2.1 to 2.6 mmol/L), and ionized calcium levels range from 4.4 to 5.2 mg/dL (1.1 to 1.3 mmol/L).

-Calcium in serum:

1) 40% bound to albumin

2) 50% free

3) 10% is bound to phosphate and citrate

Hyperparathyrodism

-Primary: increased secretion of PTH by the parathyroid gland manifested as an increase in calcium and decrease in phosphate.

-Secondary: increased serum PTH secondary to calcium wasting.

-Tertiary: persistent hyperparathyroidism after correction of secondary hyperparathyroidism resulting in autonomous PTH secretion not responsive to the negative feedback.

• Causes:

1) Adenoma (most common): 1 gland; 85%

2) Hyperplasia: 4 glands; 10%

3) Carcinoma: 1 gland; 1%

Risk factors:

1) Family history

2) MEN I, MEN IIa

3) Radiation

-Common in postmenopausal women.

Mostly sporadic.

Clinical presentation:

“Stones, Bones, Groans, and psychiatric moans”

1) Stones: kidney stones/ nephrolithiasis

2) Bones: Bone pain/ pathological fractures/ osteoporosis/ subperiostealbone resorption

3) Groans: abdominal pain/ weakness/ pancreatitis/ constipation/ gout

4) Psychiatric moans: depression/ anorexia/ weight loss/ anxiety/ emotional disturbances.

30-40% of patents asymptomatic

-X-ray findings: subperiosteal bone resorption usually in the hands and scalp .

-In adenoma, only 5% of patients have more than 1 gland involved.

-In patients with primary hyperparathyroidism due to hyperplasia, always rule out MEN syndromes.

Parathyroid carcinoma:

-may have a palpable neck mass

-Serum Ca2+ >15

-Increased PTH

-Paralysis of recurrent laryngeal nerve leading to a change in voice

-Hypercalcemic crisis

-Tumor marker: hCG

Biochemical Diagnosis

-Hypercalcemia

-Hypophosphatemia and high plasma chloride

-Elevated alkaline phosphates

-PTH Hormone value

-24 hours urine collection

Radiographs

-US

-CT

-Techtenum99 labeled Sestamibi (MIBI) isotope scans

Treatment:

Initial medical treatment for hypercalcemia consists of IV fluids and bisphosphanates. Do not use furosemide, unless the patient is overloaded.

Adenoma: surgically remove the adenoma and take biopsy of all abnormally enlarged glands

Hyperplasia: neck exploration removing all parathyroid glands and leaving at least half of parathyroid tissue placed in the forearm muscles. We leave 30mg in order to retain the parathyroid function. Moreover, if hyperparathyroidism re-occurs, we can remove some tissue from the forearm (easier access)

If carcinoma: remove the carcinoma, the ipsilateral thyroid lobe, and all enlarged lymph nodes. Modified neck dissection is indicated if lymph nodes are positive.

Surgical complications 1)Postoperative hypocalcemia:

Signs and symptoms:

-Perioral numbmess

-Parasthesia and tetany

-Chovstek’s sign

-Trouesseaus sign

2) Recurrent laryngeal nerve injury if Unilateral: voice change

if Bilateral: airway obstruction

3) Neck hematoma

4) Superior laryngeal nerve injury

Postoperative Care and Follow-Up Patients who have undergone parathyroidectomy are advised to undergo calcium level checks 2 weeks postoperatively, at 6 months, and then annually.

Recurrences are rare (<1%), except in patients with familial HPT. Recurrence rates of 15% at 2 years and 67% at 8 years have been reported for MEN1 patients

Secondary hyperparathyroidism

-Causes:

1) Renal failure ??

2) Vitamin D deficiency (Ricket’s, osteomalacia).

3) Decrease GI absorption of calcium.

-Labs:

1) Decreased calcium

2) Increased PTH

-Treatment:

1) Correct calcium and phosphate

2) Correct the underlying cause

3) No role for parathyroid surgery

Tertiary hyperparathyroidism

-Persistent hyperparathyroidism after correction of secondary hyperparathyroidism.

-Results from autonomous PTH secretion not responsive to negative feedback.

-Treatment:

1) Correct calcium and phosphate.

2) Surgical removal of the parathyroids and implanting some tissue in the

forearm, if refractory to medical treatment.

Bone disorders seen in hyperparathyroidism:

1)Renal osteodystrophy

2) Osteporosis

3) Osteomalacia

4) Ostitis fibrosa cystica

5) Brown tumors

Indications of surgery in asymptomatic hyperparathyroidism:

1) Age <50

2) Patients who cannot get appropriate follow up

3) Serum Ca >1mg above normal range

4) Urine Ca >400mg

5) 30% decrease in creatinine clearance / GFR Less than 60 cc/min

6) BY DEXA scan T score less than -2.5 at lumber spine/ total hip/ femoral neck /distal 1/3 of the radius.

Differential diagnosis of hypercalcemia :

1)Hyperparathyroidism

2)Malignancy—hematologic (multiple myeloma), solid tumors(due to PTHrP)

3)Endocrine diseases—hyperthyroidism, Addisonian crisis,VIPoma

4)Granulomatous diseases sarcoidosis,tuberculosis,berylliosis, histoplasmosis

5)Drugs—thiazide diuretics, lithium, vitamin A or D intoxication

6)Familial hypocalciuric hypercalcemia

7)Paget’s disease

8)Immobilization

Adrenals

• 1. Embryology. The adrenal cortex arises from the coelomic mesoderm around the fifth week of gestation. The adrenal medulla is populated by the neural crest cells originating from the neural ectoderm that migrate ventrally.

• 2. Anatomy. The adrenal glands are retroperitoneal structures that lie along the superior border of each kidney.

• Each adrenal gland has arterial supply from three sources, but typically only a single source of venous drainage. Arterial supply is from the superior adrenal artery which derives from the inferior phrenic artery; the middle adrenal arteries, which arise directly from the aorta; and the inferior adrenal artery, which arises from the renal artery. Venous drainage occurs through a single central vein for each adrenal; the right adrenal vein drains directly into the IVC and the left adrenal vein drains into the left renal vein.

• 3. Physiology. The adrenal gland is histologically composed of four layers, each with their own biosynthetic products.

• a. Adrenal cortex

• The zona glomerulosa is responsible for mineralocorticoid production, of which aldosterone is the primary product. Aldosterone production is stimulated by angiotensin II and increased levels of serum potassium. Aldosterone acts to increase circulating blood volume by increasing sodium and chloride reabsorption in the distal tubule of the kidney.

• The zona fasciculata produces the glucocorticoids, of which cortisol is the primary product. Cortisol production is stimulated by the release of adrenocorticotropic hormone (ACTH) by the anterior pituitary gland. ACTH itself is stimulated by the release of corticotropin-releasing hormone (CRH) by the hypothalamus. Glucocorticoids have extremely broad effects with the overall goal of inducing a catabolic state in the body in response to stress. Glucocorticoids increase blood glucose concentrations, stimulate lipolysis, enhance adrenergic stimulation of the cardiovascular system, and reduce the inflammatory response of the immune system.

• The zona reticularis produces the adrenal sex hormones androstenedione and dehydroepiandrosterone (DHEA). These hormones support the gonadal production of testosterone and estrogen.

• b. Adrenal medulla

The medulla produces the catecholamines norepinephrine and epinephrine that act on peripheral α- and β-adrenergic receptors. α-Receptor stimulation produces peripheral vasoconstriction. β1-Receptor stimulation targets the myocardium and increases heart rate and contractility. β2-Receptor stimulation produces peripheral vasodilation.

•Laboratory diagnosis.

Screening for hyperaldosteronism consists of measurement of upright plasma aldosterone concentration (PAC) and plasma renin activity (PRA). A PAC:PRA ratio of >25–30 in conjunction with a primary aldosterone level >15 ng/dL and plasma renin <0.5 ng/mL/hr is diagnostic of primary hyperaldosteronism. Drugs that stimulate renin such as spironolactone, angiotensinconverting enzyme (ACE) inhibitors, and angiotensin receptor antagonists (ARBs) can produce false-negative test results. β- Blockers, clonidine, and nonsteroidal anti-inflammatory drugs suppress renin and may result in false positives.

• Localization.

Once the biochemical diagnosis has been established, the subtype of hyperaldosteronism should be determined. (1) High-resolution thin-cut (3-mm) adrenal CT may show a unilateral adenoma with better spatial resolution than MRI. It is important to note that incidental adrenal nodules are more common with increasing age and that, while aldosterone-producing adenomas are treated by surgical excision, bilateral hyperplasia is treated medically. Therefore, older patients and those with microadenomas as well as those with normal adrenals and bilateral nodules should undergo adrenal vein sampling (AVS) to determine if there is a unilateral increased source of aldosterone before proceeding to surgery.

•In AVS, simultaneous adrenal vein blood samples for aldosterone and cortisol are taken from both adrenal veins and the IVC. An aldosterone to cortisol ratio greater than 4:1 between sides supports a lateralizing source and management by adrenalectomy.

•Tx by surgical removing of APA. It is critically important to stop spironolactone and any potassium diuretics once adrenalectomy has been performed in order to avoid severe hyperkalemia postoperatively. Plasma aldosterone and renin should be measured at follow-up to document biochemical cure.

• Biochemical testing. The biochemical diagnosis of pheochromocytoma is made by demonstrating elevated levels of plasma metanephrines or 24-hour urinary catecholamines and metanephrines.

• Localization.

Radiographic tests are used to demonstrate the presence of an adrenal mass.

(1) CT identifies 90% to 95% of pheochromocytomas >1 cm.

(2) In patients with biochemical evidence pheochromocytoma and negative CT and MRI, further imaging with scintigraphic or PET scanning can help identify occult tumors. Scintigraphic scanning after the administration of 123I-metaiodobenzylguanidine (MIBG) provides a functional and anatomic test of hyperfunctioning chromaffin tissue. MIBG scanning is very specific for both intra-and extra-adrenal pheochromocytomas but is expensive and somewhat difficult to use.

•The treatment of benign and malignant pheochromocytomas is surgical excision.

•Preparation for adrenalectomy for pheochromocytomas includes administration of α-adrenergic blockade to control hypertension and to permit reexpansion of intravascular volume. Phenoxybenzamine is a nonspecific α- blocker that is initiated and increased to 20 to 40 mg orally two to three times per day until the desired effect or prohibitive side effects are encountered. However, its use today is limited by the high cost of the medication (e.g., $9,000 for 100 10-mg capsules). Consequently, selective α-blockers such as doxazosin and calcium channel blockers are increasingly being used given their low cost and more favorable side effect profiles.

•β-Adrenergic blockade (e.g., metoprolol) may be added if reflex tachycardia or arrhythmias develop but should only be initiated after complete α- adrenergic blockade to avoid unopposed α-effect and precipitation of a hypertensive crisis.

• Intra-operative considerations: All patients should be monitored intraoperatively with an arterial line. Patients with large or very active pheochromocytomas, or who have significant comorbidities, may require central line placement.

•Following pheochromocytoma excision, annual follow-up with measurement of plasma fractionated metanephrines is recommended for at least 5 years after adrenalectomy because of the risk of recurrence, even after resection of an apparently benign lesion.

Nonfunctional Adrenal Masses

• Adrenocortical adenomas

• Adrenal myelolipoma

• Adrenocortical carcinoma (ACCA)

• Adrenal metastases

are the most common malignant lesions involving the adrenal gland. Frequently, bilateral lesions are present.

Lung, breast, melanoma, colorectal, pancreatic, hepatocellular, and renal cell cancers all may metastasize to the adrenal glands.