Stig Valdemarsson

Persistent elevated serum levels of intact parathyroid hormone after operation for sporadic parathyroid adenoma: Evidence of detrimental effects of severe parathyroid disease*

BACKGROUND A significant number of patients with primary hyperparathyroidism (pHPT) who are surgically treated have increased serum levels of intact parathyroid hormone (PTH) during long-term follow-up despite normocalcemia. The cause and significance of this finding remain to be established. METHODS A total of 82 patients operated on for sporadic parathyroid adenoma were investigated before and at 8 weeks and 1 year after operation with serum levels of intact PTH, bone mineral content, and biochemical variables known to reflect PTH activity. RESULTS All patients had low or normal serum levels of calcium during follow-up. At 8 weeks after operation 20 (24%) patients had increased serum levels of PTH. These patients had severe parathyroid disease and low levels of 25(OH) vitamin D before operation. In contrast to patients with normal levels of PTH after operation, they did not have an elevated bone mineral content but had elevated levels of serum creatinin. At 1 year after operation 13 patients had elevated serum levels of PTH. Compared with patients with normal serum levels of PTH, they were older and had an increased frequency of cardiovascular disease and biochemical indications of compromised renal function. They did not have an elevated bone mineral content. CONCLUSIONS Persistently increased serum levels of PTH indicate harmful effects of pHPT even after surgical cure, especially in elderly patients with severe disease before operation. The results in this investigation therefore favor early treatment of pHPT.

Metabolic abnormalities related to cardiovascular risk in primary hyperparathyroidism: effects of surgical treatment.

Valdemarsson S, Lindblom P, Bergenfelz A (Departments of Internal medicine and surgery, Lund University Hospital, Lund Sweden). Metabolic abnormalities related to cardiovascular risk in primary hyperparathyroidism: effects of surgical treatment. J Intern Med 1998; 244: 241–49.

Reversal of decreased hepatic lipase and lipoprotein lipase activities after treatment of hypothyroidism

Abstract. Plasma lipoprotein concentrations, activities of hepatic lipase and lipoprotein lipase in post‐heparin plasma, and the removal rate of exogenous triglyceride were measured in fourteen patients with severe primary hypothyroidism before and after 4 months substitution therapy with 1‐thyroxine. Before treatment plasma LDL cholesterol concentrations were markedly increased while HDL cholesterol and plasma triglycerides were in the upper reference range. Thyroxine substitution led to a normalization of LDL cholesterol in all patients. Plasma triglycerides and HDL cholesterol decreased moderately. Hepatic lipase and lipoprotein lipase activities were initially reduced but increased significantly after treatment, by about 170% and 55%, respectively. The increase in hepatic lipase activities was significantly correlated to the increase in serum triiodothyronine levels and also to the reduction in LDL cholesterol concentrations. The decrease in LDL cholesterol was also significantly correlated to the increase in serum triiodothyronine concentration.

Fatigue after aneurysmal subarachnoid hemorrhage evaluated by pituitary function and 3D-CBF.

Objective – The reason for longstanding fatigue following aneurysmal subarachnoidal hemorrhage (SAH) is still not clarified. The bleed from supratentorial aneurysms is often in the vicinity of the hypothalamus and pituitary gland making an endocrine dysfunction plausible.

Congestive heart failure: involvement of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibres

Abstract. In controls and in patients suffering from congestive heart failure (CHF) the circulating levels of catecholamines, neuropeptide Y‐like immunoreacti‐vity (NPY‐LI), vasoactive intestinal peptide‐LI (VIP‐LI), substance P‐LI (SP‐LI) and calcitonin gene‐related peptide‐LI (CGRP‐LI) markers of sympathetic, parasympathetic and sensory nervous systems, respectively, have been examined. There was a significant rise in the levels of noradrenaline, NPY‐LI and SP‐LI already in moderate CHF (New York Heart Association Stage I and II). In patients with severe CHF (NYHA Stage III and IV) the circulating levels of noradrenaline, adrenaline, NPY‐LI and SP‐LI were significantly increased. CGRP‐LI was not altered, despite the fact that this peptide co‐exists in many tissues with SP. There was no change in VIP‐LI. The pathophysiological significance of this pattern of reaction of circulating catecholamines and neuropeptides is unclear; however, the rise in SP‐LI may be a reaction to counterbalance the vasoconstrictive effects of the activation of the sympatho‐adrenal system.

Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease

Valdemarsson S, Lindergård B, Tibblin S, Bergenfelz A (Lund University Hospital, Sweden). Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease. J Intern Med 1998; 243: 115–22.

Postoperative Elevated Serum Levels of Intact Parathyroid Hormone after Surgery for Parathyroid Adenoma: Sign of Bone Remineralization and Decreased Calcium Absorption

Increased levels of intact parathyroid hormone (PTH) have been documented after surgery for primary hyperparathyroidism (pHPT) despite normocalcemia. The pathogenesis remains to be elucidated. Seventeen consecutive patients operated on for solitary parathyroid adenoma were investigated before and at 8 weeks and 1 year after surgery with serum levels of intact PTH, biochemical variables known to reflect PTH activity, and bone mineral content (BMC). In addition, an oral calcium loading test was performed 8 weeks after the operation. All patients had low or normal serum calcium levels during follow-up. Eight weeks after operation six patients (35%) had an increased serum PTH level. These patients (group I) preoperatively had higher serum levels of PTH and alkaline phosphatase than patients with normal PTH levels (group II). They also had lower BMC and larger parathyroid adenomas. They did not differ in renal function. At 8 weeks after operation group I showed higher mean serum levels of osteocalcin and propeptide of type I procollagen but lower urinary calcium excretion. In contrast to patients in group II, they also showed a lower calciuric response and a trend to a lower calcemic response during the oral calcium load. The two groups showed similar parathyroid sensitivity for calcium. Patients in group I demonstrated a significant increase in BMC the first year after the operation. Increased serum PTH 8 weeks after surgery for sporadic parathyroid adenoma was not due to persistent pHPT or impaired renal function. Instead, the results imply there is diminished calcium absorption and increased bone turnover with cortical bone remineralization.

Hormonal influence on calcitonin gene-related peptide in man: effects of sex difference and contraceptive pills.

Calcitonin gene-related peptide (CGRP) is one of the peptides encoded for by the calcitonin gene. It has been demonstrated in man to be located in the thyroid and in perivascular nerves and to possess potent vasodilatory properties. In the present study we found plasma levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) to be significantly higher in females than in males and that women on contraceptive pills had significantly higher CGRP-LI levels than women not taking contraceptives. These data are in accordance with one earlier report on an increased CGRP level during pregnancy and suggest a positive influence of the female sex hormones on the plasma CGRP level in man, which should be considered in the establishment of a reference range for this analysis.

Primary aldosteronism among newly diagnosed and untreated hypertensive patients in a Swedish primary care area.

Abstract Objective. To evaluate the prevalence of primary aldosteronism (PA) in newly diagnosed and untreated hypertensive patients in primary care using the aldosterone/renin ratio (ARR), and to assess clinical and biochemical characteristics in patients with high and normal ARR. Design. Patient survey study. Setting and subjects. A total of 200 consecutive patients with newly diagnosed and untreated hypertension from six primary health care centres in Sweden were included. Main outcome measures. ARR was calculated from serum aldosterone and plasma renin concentrations. The cut-off level for ARR was 65. Patients with an increased ARR were considered for confirmatory testing with the fludrocortisone suppression test (FST), followed by adrenal computed tomographic radiology (CT) and adrenal venous sampling (AVS). Results. Of 200 patients, 36 patients had an ARR > 65. Of these 36 patients, 11 patients had an incomplete aldosterone inhibition during FST. Three patients were diagnosed with an aldosterone producing adenoma (APA) and eight with bilateral adrenal hyperplasia (BHA). Except for moderately lower level of P-K in patients with an ARR > 65 and in patients with PA, there were no biochemical or clinical differences found among hypertensive patients with PA compared with patients without PA. Conclusion. Eleven of 200 evaluated patients (5.5%) were considered to have PA. The diagnosis of PA should therefore be considered in newly diagnosed hypertensive subjects and screening for the diagnosis is warranted.

Increased plasma level of substance P in patients with severe congestive heart failure treated with ACE inhibitors

Abstract. The effects of angiotensin‐converting‐enzyme (ACE) inhibitors on circulatory regulating mechanisms in congestive heart failure (CHF) were studied by comparison of plasma levels of catecholamines, neuropeptide Y‐like immunoreactivity (NPY‐LI), substance P (SP‐LI), calcitonin gene‐related peptide (CGRP‐LI), vasopressin (ADH‐LI), atrial natriuretic peptide (ANP‐LI) and renin activity (PRA) in patients with severe CHF (NYHA III‐IV) with (n = 15) or without (n = 17) ACE inhibitors in addition to digoxin and diuretic therapy. Data were also compared with those for healthy subjects (n = 31) and patients with moderate CHF (NYHA I‐II). Catecholamines and NPY‐LI were increased to the same extent in both groups with severe CHF. CGRP‐LI showed no changes relative to controls in any of the patient groups, and was not affected by ACE inhibitors. The SP‐LI level was significantly increased in all patient groups. Patients with severe CHF on ACE inhibition had a SP‐LI level of 4.05±0.79 pmol l−1, compared to a concentration of 2.28±0.30 pmol l−1 (P < 0.05) in the patient group with a comparable degree of CHF but without ACE inhibition. In the latter group, an inverse relationship appeared between the SP‐LI and the serum sodium levels (r = —0.68, P < 0.05). The patients with severe CHF who received ACE inhibitors had significantly lower ADH‐LI levels than the patients with a comparable degree of CHF who were not treated with ACE inhibitors, while the ANP‐ LI level was increased to a similar extent in both groups.