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Endocrine Disorders E Panieri Dm Dent OPEN ACCESS TEXTBOOK OF GENERAL SURGERY ENDOCRINE DISORDERS E PANIERI DM DENT system, pancreas, testis, and INTRODUCTION placenta).PTH ½ life is approximately 4 minutes. Certain endocrine disorders are PTH increases blood calcium levels by managed surgically: the most common stimulating osteoclasts to break down are disorders of the thyroid gland (see bone and release calcium. PTH also Chapter Thyroid Gland) and less increases gastrointestinal calcium commonly are those of the parathyroid absorption by activating vitamin D, and gland, adrenal gland and certain rare promotes calcium conservation islet cell lesions of the pancreas. (reabsorption) by the kidneys. PTH also regulates serum phosphate There are fundamental processes that concentrations via actions on the all have in common: Clinical kidney. awareness and recognition, biochemical confirmation, anatomical Anatomy localization, selection for surgery, There are typically 4 parathyroid surgical operation and the sequelae. glands; however, supernumerary Close co-operation between the glands and fewer than four glands surgeon and endocrinologist or have been reported. In the majority of physician provide optimal patient care. cases the parathyroids are symmetrically located in the neck in This chapter will deal with surgical close relationship to the posterior pathologies related to the parathyroid aspect of the thyroid (Fig1). glands, the adrenal, endocrine tumours of the pancreas and GIT, as well as rare inherited syndromes PARATHYROID GLANDS Ext Carotid artery Physiology The major function of the parathyroid Sup thyroid art glands is to maintain the body's Inf constrictor calcium and phosphate levels within a Cricothyroid very narrow range, so that the nervous and muscular systems can function Parathyroids properly. The parathyroid glands do this by secreting parathyroid hormone. Inf thyroid art PTH is a polypeptide containing 84 RLNs amino acids. It acts to increase the concentration of Ca2+ in the blood, Oesophagus whereas calcitonin (a hormone Thyrocervical produced by the parafollicular cells (C trunk cells) of the thyroid gland) acts to decrease Ca2+ concentration. PTH Figure 1: Posterior view of the thyroid acts to increase the concentration of gland demonstrating parathyroids, the RLNs and the superior and inferior thyroid calcium in the blood by acting upon arteries the PTH1 receptor (high levels in bone and kidney) and the PTH2 receptor (high levels in the central nervous 2 Types of hyperparathyroidism Disorders of parathyroid glands Hyperparathyroidism (HPT) is a Primary hyperpararthyroidism * condition of excess secretion of Long term Lithium Rx parathyroid hormone from the Familial hypocalciuric hypercalcaemia parathyroid glands. Malignancy Haematological malignancy PRIMARY Bone metastases HYPERPARATHYROIDISM Paraneoplastic syndrome This is the most common form of Vit D disorders hyperparathyroidism encountered. The Hypervitaminosis D disease is caused by abnormalities in sarcoidosis the parathyroid glands. The usual High bone turn over pathology is of a single adenoma. The Thyrotoxicosis aetiology is not clear, and the cause of Long term bed rest the adenoma is unknown. In a small Thiazides proportion (approximately 5%) of Vit A cases all 4 glands have hyperplasia. Multiple myeloma The latter may be associated with Renal disorders MEN syndrome, with a genetic Tertiary hyperparathyroidism mutation located on chromosome 11. Milk-alkali syndrome Aluminium intoxication The excess secretion of parathyroid hormone (PTH) results in Table 1- Causes of hypercalcaemia. hypercalcaemia, and the consequent 90% are caused by primary features of the disease. hyperparathyroidism or malignant disease PTH stimulates the osteoclast and promotes bone re-absorption, Hypercalcaemia (>2.6 mmol/L) and its producing the characteristic bone implications is frequently missed in changes, and releasing calcium, clinical practice. Every case of phosphate and alkaline phosphatase. hypercalcaemia requires a clinical The calcium and phosphate are explanation. presented in excess to the kidney and into the urine, which may result in Clinical Features stone formation. Although PTH The clinical presentations of primary promotes calcium absorption and hyperparathyroidism are often subtle, phosphate loss in the renal tubule, the and may go unrecognized. Awareness excess calcium “spills over”. The of the condition is critical to the hypercalcaemia may affect many diagnosis. organs including the brain. It is not unusual for hypercalcaemia Primary hyperparathyroidism is the symptoms of hyperparathyroidism to most common cause of be non-specific and vague and hence hypercalcaemia in a non-hospital is often underestimated. Typical population. In a hospital population, presentations include recurrent renal however, malignant disease makes up calculi, progressive bone density loss at least half the cases. In the past, and occasionally pathological certain calcium containing ulcer fractures, ill-defined musculo-skeletal medications taken with milk (“milk complaints, neuro-cognitive alkali syndrome”), and excessive impairment, and unexplained administration of cod liver oil and abdominal pain. Bone, stones, groans vitamin D (hypervitaminosis D) and moans is a helpful mnemonic to produced hyper-calcaemia: These are the effects of the disease. no longer encountered. 3 In addition to these modes of The most accurate of these is a presentation, hypercalcaemic crisis sestaMIBI scan, performed by Nuclear (dysequilibrium hypercalcaemia) may Medicine. present as a fulminating emergency with rapidly rising calcium levels, Ultrasonography is a helpful adjunct in polyuria and dehydration, and selected cases. CT scan, MRI, venous subsequent confusion, coma and sampling are very seldom performed. death. This emergency requires major rehydration, hypocalcaemic drugs and urgent surgery. Bones: Radiological and densitometric abnormalities Musculoskeletal pain/”fibromyalgia”/ “arthritis” Pathological fractures Von Recklinghausen disease Stones: Renal stones are common Groans: Abdominal pain from renal stones is common; Association with pancreatitis and peptic ulcer are questioned. Moans: Depression is common ?Alzheimers Figure 1- Sestamibi scan showing a Tiredness/ apathy focus of parathyroid activity below the Confusion in hypercalcaemic crisis right pole of the thyroid gland, in Delirium keeping with an adenoma at that site. Asymptomatic: Pathology Associations Diagnostic A significant number present with incidental tests hypercalcaemia Primary hyperparathyroidism Table 2- Clinical features of primary Adenoma Sporadic (95%) 2+ hyperparathyroidism MEN syndrome ↑ sCa Hyperplasia ↑ sPTH (5%) Diagnosis normal PO4- ↑ urineCa2+ The diagnosis is made from the clinical features (eg: renal stones) and the Secondary hyperparathyroidism biochemical confirmation. Many cases Hyperplasia Renal failure are asymptomatic, and the only clue to GIT normal Ca2+ the diagnosis is unexplained malabsorption ↑ PTH ++++ hypercalcaemia. The diagnosis usually ↑ PO4- rests on two simple blood tests: Tertiary hyperparathyroidism elevations of the serum calcium and Hyperplasia Renal failure parathyroid hormone. ↑ Ca2+ ↑ PTH ++++ When, however, the biochemical ↑ PO4- diagnosis has been made and surgery is indicated, special localising studies Table 3- diagnostic features of different are performed to guide the surgeon to types of hyperparathyroidism the most likely site of the adenoma. 4 Treatment absorption (which is vitamin D Surgery is undertaken in most cases: mediated), decreased levels of vitamin the single adenoma is removed, or in D, due to absent renal hydroxylation of the case of 4 gland hyperplasia, 3½ calciferol, and perhaps PTH resistance glands are removed. Asymptomatic in bone. Phosphate retention and the patients are submitted to surgery falling calcium levels stimulate the unless they have a severe medical parathyroid glands (hyperplasia), and contra-indication as they may proceed the excessive levels of PTH then to renal damage, osteopaenia or stimulate osteoclast activity causing psychological abnormality in later life. osteopaenia. The majority of parathyroid operations The clinical picture is that of a patient are simple, quick and very rewarding in chronic renal failure who develops for both surgeon and patient. However osteopaenia with elevated alkaline on occasion parathyroid glands may phosphatase and PTH levels. Other be infuriatingly difficult to identify and symptoms are pruritus, pathologic may test the skill and patience of the bone fractures, ectopic soft tissue most experienced endocrine surgeon. calcification, severe vascular Parathyroidectomy is best performed calcification, and bone pain or skin by centers who are well versed with ulcers. these complexities. The surgical management is to remove 3½ of the hyperplastic glands. The fourth gland remainder may be left in situ or transplanted into the forearm for easy access should it be become overactive again. TERTIARY HYPERPARATHYROIDISM In some patients the process may become autonomous, typically after a Figure 2- Typical 3cm parathyroid successful renal transplant removes adenoma adjacent to surgical site. the hypocalcaemic stimulus; this is SECONDARY then labelled tertiary hyper- HYPERPARATHYROIDISM parathyroidism, and the patient becomes hypercalcaemia again, with Secondary and tertiary the danger of renal calculi to the new hyperparathyroidism may arise in transplanted kidney patients with chronic renal failure (or very rarely in GIT malabsorptive
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