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Review Article | DOI: https://doi.org/10.31579/2690-8794/155
Department of Surgery, Faculty of Health Sciences, University of Buea, Cameroon, W/Africa
*Corresponding Author: Weledji EP, Diagnosis and Treatment Center „Dr Victor Babes”, Bucharest, Romania
Citation: Weledji EP. (2023), Parathyroid Gland Disease: an Intricate Interaction Between Physiology and Surgery, Clinical Medical Reviews and Reports. 5(1); DOI:10.31579/2690-8794/155
Copyright: © 2023, Weledji EP. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 04 March 2023 | Accepted: 16 March 2023 | Published: 27 March 2023
Keywords: hyperparathyroidism; calcium; homeostasis; parathyroid hormone; vitamin D; surgery; multiple endocrine neoplasia
Diseases are essentially disorders of physiological function. However, most patients with hyperparathyroidism are discovered incidentally during routine biochemical screening that includes a serum calcium determination. As patients with chronic renal failure now live longer as a result of dialysis and renal transplantation, secondary hyperparathyroidism is becoming more common. The management requires the understanding of the physiology of calcium homeostasis and implications in the human body. The aim of surgery is to remove the abnormal glands and leave the patient normocalcaemic. The familial multiple endocrine neoplasia (MEN) syndrome often present with parathyroid hyperplasia and screening by hormonal and biochemical analysis is mandatory once an index case has been identified.
Many diseases are natural experiments which can be of great value in showing how variables and systems act upon each other. Physicians recognize and distinguish diseases by symptoms and signs which are further disorders of function revealed by close observation or elicited by testing routines. Calcium is the most abundant cation in the human body, there being about 25moles (1kg), in an average 70 kg man. Almost all of this calcium is within bone, which consists essentially of complex salts of calcium and phosphate. However, both calcium and phosphorus (as phosphate) have important extra-skeletal functions. Parathyroid gland disease is mostly manifested as hyperparathyroidism. The elucidation of the aetiology of hyperparathyroidism is based upon understanding the physiology of calcium (Ca 2+) homeostasis and its importance in the human body. The short, medium/long-term control of calcium ion in the body is by the peptide parathyroid hormone, (PTH) and the steroid hormone Vitamin D. Calcitonin, a peptide hormone secreted by the parafollicullar C- cells of the thyroid gland which acts on bone to reduce the release of Ca 2+ to the ECF during episodes of hypercalcaemia may be protective against such abnormal rises but it does not seem to play any significant role in normal Ca 2+ control. There are usually 4 parathyroid glands, occasionally 3 or 5, anatomically arranged in pairs. The superior pair on the posterior surface of the thyroid gland developed from the fourth branchial pouch is intricately related to the recurrent laryngeal nerve as it courses under the inferior thyroid artery, but the inferior pair close to the lower pole and together with the thymus develop from the third pharyngeal pouch is mostly variable in position (anterior mediastinum, the thymus (10%), within the carotid sheath and intracapsular thyroid itself) may explain the cause of the ‘failed neck exploration’ (Fig 1). PTH is normally secreted in response to a lowering of the serum ionized calcium (n: 2.2-2.7mmol/l) by mobilizing calcium from bone and by encouraging calcium resorption and phosphate excretion at the renal tubule to keep constant the solubility product of calcium phosphate in the extracelluar fluid (ECF) for its important physiological activities. It also hydroxylates the 1 α part of the inactive vitamin D3 to the active 1, 25-dihydroxycholecalciferol at the renal tubule [1]. Activated vitamin D acts by increasing calcium and phosphate absorption from the gut for the medium and long-term control of total body calcium especially in children, during pregnancy and lactation where there are additional requirements for calcium [2]. The importance of the tightly controlled free extracellular Ca2+ which is the biologically- active fraction is because several vital processes are dependent on the appropriate calcium concentration: a) neuromuscular excitability: with a fall in Ca2+, excitable tissues become easier to stimulate which may be fatal due to cardiac arrhythmias, laryngeal spasm and respiratory arrest. These also result from increased permeability to sodium ions and membrane potential depolarization. By the same mechanism high [Ca 2+] depresses nerve and muscle activity; b) excitation-contraction coupling: since contraction depends on an increase in intracellular [Ca 2+] any decrease may reduce the strength of contraction in cardiac and smooth muscle; c) stimulus- secretion coupling: the release of secretory substances such as hormones and neurotransmitters depends on Ca 2+ entry following stimulation of the cell, and d) blood clotting is calcium dependent [3].
Figure 1. Schematic diagram of the topography of the parathyroid glands
Figure 2. Schematic diagram of a parathyroid adenoma
Thus, the pathological overproduction of PTH depending on the cause is divided into three groups: primary (most common) secondary and tertiary. Primary hyperparathyroidism (10 HPT) characterized by a persistently elevated calcium and a low serum phosphate must be due to an autonomous production of PTH i.e. parathyroid adenoma (85%), parathyroid gland hyperplasia (10%) or a parathyroid carcinoma (2%). These are not inhibited by the prevailing circulating high Ca2+ level. Although the clinical features of primary hyperparathyroidism are due to hypercalcaemia, most patients are diagnosed incidentally during routine biochemical screening that involves serum calcium determination with the highest incidence in post menopausal women. Many patients present with a complex of symptoms caused by long-standing hyperparathyroidism including muscle weakness (myopathy) and arthralgia, peptic ulcer disease (increased gastrin secretion), abdominal pain and constipation, renal calculi, psychiatric disorders, hypertension and the rare corneal band keratopathy. This is summarized with the well known tetrad of ‘stones’, ‘bones’, ‘moans’ and ‘abdominal groans’. The diagnosis is confirmed with biochemical test as a high serum calcium level coupled with a low serum phosphate is highly suggestive. An elevated serum PTH level coupled with a raised urinary calcium excretion completes the diagnosis. However, a normal serum intact PTH in the setting of hypercalcaemia does not rule out the disease [4]. In long-standing disease several radiological changes occur including subperiosteal bone resorption in the phalanges, generalized skeletal demineralization (‘pepperpot’ skull, osteitis fibrosa cystic, etc), renal calculi or nephrocalcinosis. Distinction must be made between other causes of hypercalcaemia such as metastatic skeletal carcinomatosis, sarcoidosis, myeloma, milk-alkali syndrome, vitamin D intoxication, tuberculosis (TB), thiazide diuretics, Paget’s disease. Protein electrophoresis (myeloma), bone scan, skeletal survey, parathyroid hormone assays, urinary calcium excretion, the Kveim and Tuberculin tests, if indicated should exclude the other causes. In a fit patient, surgery is treatment of choice even when the disease is asymptomatic. Without pre-operative imaging parathyroid exploration is a demanding operation due to difficulty in gland location with risk of failed neck exploration, recurrent laryngeal nerve injury (Figure 1), and post-operative hypocalcaemia. Infusion of methylene blue (5mg/kg in 500ml of 5
Many diseases are natural experiments and thus the important corollary to the physician’s ability to recognize and evaluate the abnormal, and take intelligent action to prevent, compensate for, and cure departures from normality. The management of parathyroid gland disease requires the understanding of the physiology of calcium homeostasis and implications in the human body. The clinical manifestations of hyperparathyroidism may be non-specific and thus require a high level of clinical suspicion. The aim of surgery is to remove the abnormal glands and leave the patient normocalcaemic. Patients presenting with primary hyperparathyroidism also represent a population at increased risk of the MEN syndrome.
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