L. Cantalamessa

Psychopathological and cognitive features in subclinical hypothyroidism

1. To evaluate effective and cognitive dysfunctions in subjects with a marginal form of thyroid hypofunction the authors studied a population of female goiter patients, divided in two groups on the basis of thyroid function: euthyroidism and subclinical hypothyroidism (SCH). 2. The SCH patients were treated with levothyroxine (LT4) in order to obtain euthyroidism, as demonstrated by normalization of the hormonal pattern. 3. Both groups were evaluated with a wide range of psychometric tests (Wechsler memory test, scribble test, reaction times) and psychopathological rating scales (Hamilton rating scales for depression and anxiety, brief psychiatric rating scale) at admission and after 3 months. 4. At admission, a significant decrease in logical memory was found in SCH patients; no differences in affectivity ratings were found between the groups. 5. After LT4 treatment, SCH patients showed a significant improvement in some items of memory performance. 6. In conclusion, when interfering factors relating to the perception of disease were excluded by employing euthyroid goiter patients as a comparison group, SCH appeared associated only with memory impairment, while the impairment of affective functions described in previous studies comparing SCH patients with normal controls was not confirmed. A significant improvement of memory skills was induced by LT4 treatment in SCH patients.

Inhibitory effect of calcitonin on growth hormone and insulin secretion in man

The effect of calcitonin administration on basal and arginine-stimulated growth hormone and insulin plasma levels was investigated. The intramuscular injection of synthetic salmon calcitonin (100 U MRC) in five normal subjects produced a significant decrease (p less than 0.05) in insulin concentration. The same amount of calcitonin given 15 min before an arginine infusion test in seven normal subjects significantly reduced the response of growth hormone (p less than 0.025) and insulin (p less than 0.005) to the stimulus.

Effect of somatostatin on blood glucose, plasma growth hormone, insulin, and free fatty acids in normal subjects and acromegalic patients

Abstract Synthetic growth-hormone-release inhibitory hormone (GRIH, somatostatin) infused in seven acromegalics significantly lowered plasma growth hormone (GH) and immunoreactive insulin (IRI) levels, did not have any effect on blood glucose, and significantly increased plasma free fatty acids (FFA). Somatostatin, when infused in three normal subjects during an arginine test, inhibited plasma GH and IRI responses. Hypoglycemia-induced GH release was also blocked by somatostatin in two normal subjects thus tested.

Plasma ACTH-response to the corticotropin releasing factor in patients with Cushing's disease. Comparison with the lysine-vasopressin test

In three female patients with Cushings disease, 100 micrograms of synthetic ovine corticotropin releasing factor (CRF) were administered before surgery and 1 week after transsphenoidal microadenomectomy. In these patients a test with lysine-vasopressin (LVP), 10 U intramuscularly, was also performed before and after pituitary surgery. Before surgery, both stimuli induced a clear increase in plasma ACTH and cortisol in all patients; the response of ACTH to CRF was of greater magnitude. Postoperatively, the responses were virtually absent in two patients, but were still present in the third one in whom the removal of adenoma had been partially unsuccessful. The CRF test was also performed in a female patient with Cushings syndrome due to adrenal adenoma; in this patient no responses of plasma ACTH and cortisol to CRF were recorded. This paper demonstrates that pituitary microadenomas causing Cushings disease may retain the ability to respond to CRF; this stimulus may be useful in the differential diagnosis between ACTH-dependent and independent Cushings syndrome; the lack of response after microadenomectomy indicates successful removal of the tumor. CRF is more potent than LVP in releasing ACTH at the doses employed.

Autocrine inhibitory influences of α-melanocyte-stimulating hormone in malignant pleural mesothelioma

Malignant pleural mesothelioma is a highly aggressive tumor arising from the mesothelial cells that line the pleural cavities. This tumor is resistant to most conventional anticancer treatments and appears to be very sensitive to growth‐promoting influences of cytokines and growth factors. Identification of natural inhibitory pathways that control growth should aid discovery of novel therapeutic approaches. We hypothesized that α‐melanocyte‐stimulating hormone (α‐MSH), which is produced by many cell types and antagonizes cytokines and growth factors, could be an endogenous inhibitory molecule in mesothelioma. Twelve mesothelioma cell lines were established from pleural effusions of patients with malignant mesothelioma. Mesothelioma cells were found to express mRNA for proopiomelanocortin and its processing enzymes; release α‐MSH peptide into supernatants; and express melanocortin 1 receptor (MC1R), the high‐affinity receptor for α‐MSH. Immunoneutralization of MC1R in the cell lines enhanced expression of interleukin‐8 (IL‐8), IL‐6, and transforming growth factor‐β. These molecules promote mesothelioma proliferation and are considered therapeutic targets in this tumor. Coincubation of mesothelioma cells with synthetic α‐MSH significantly reduced cell proliferation. The present research shows an autocrine‐inhibitory circuit based on α‐MSH and its receptor MC1R. Activation of MC1R by selective peptides or peptidomimetics might provide a novel strategy to reduce mesothelioma cell proliferation by taking advantage of this endogenous inhibitory circuit.

A black adrenocortical adenoma causing Cushing's syndrome not imaged by radiocholesterol scintigraphy

In a 33-year-old female patient with left adrenal tumour and Cushings syndrome, adrenocortical scintigraphy with radiocholesterol did not image the tumour nor the suppressed contralateral gland. Histology showed a black adrenocortical adenoma composed only of compact cells; there was no evidence of malignancy. This demonstrates that non-visualization of the adrenal glands in a patient with Cushings syndrome is not invariably due to adrenal carcinoma. The literature on black adrenal adenomas causing Cushings syndrome is reviewed.

A singular case of graves' disease in congenital thyroid hemiagenesis

We report the observation of an unusual case of Graves’ disease associated with thyroid hemiagenesis. A 41-year-old woman who presented with symptoms and clinical signs of hyperthyroidism was discovered to have thyroid hemiagenesia of the left lobe. Thyroid ultrasound scan showed enlargement of the right lobe with a single nodule, and absence of the left lobe; isotope scan showed homogeneous uptake in the single lobe and nodule. Ophthalmopathy, which was absent at presentation, developed after two years; after a further 2 years the patient developed decompensated hypothyroidism requiring thyroxine replacement. This is the first case of Graves’ disease in thyroid hemiagenesis evolved to hypothyroidism, and a rare case of thyroid ophthalmopathy accompanying this condition.

Increased growth hormone response to growth hormone releasing hormone induced by erythropoietin in uraemic patients

This study was designed to assess the response of growth hormone (GH) to growth hormone releasing hormone (GHRH) and the possible interaction of acutely administered recombinant human erythropoietin (rhEPO) on GH response to GHRH in a group of uraemic patients. Eight patients on maintenance haemodialysis, not previously treated with rhEPO, and six healthy controls were tested with GHRH (100 μg i.v. in bolus), and with GHRH (100 μg i.v. in bolus) plus rhEPO (40 U/kg in constant infusion for 30 min) on different days. GHRH injection provoked a GH release in five out of eight uraemic patients; the overall mean response did not differ significantly from the GH response obtained in controls (P = 0.30). Erythropoletin infusion significantly increased GH release after GHRH (P > 0.01 at 15, 30, 45, 60 min after GHRH injection) in uraemic patients; in controls, on the contrary, stimulation with GHRH plus rhEPO did not induce a greater increase of OH release compared with that observed after GHRH alone (mean GH peak 37.66 |Mp 7.68 mU/I after GHRH; and 38.0 |Mp 9.18 mU/I after GHRH plus rhEPO; P < 0.5). In this study acutely administered rhEPO significantly potentiated the GH response to GHRH in uraemic patients whereas the same effect was not demonstrable in subjects with normal renal function.

Cushing’s Syndrome due to Unilateral Adrenal Nodular Hyperplasia with Incomplete Inhibition of the Contralateral Gland

A 57-year-old woman was demonstrated to be affected by adrenocorticotropic hormone (ACTH)-independent Cushings syndrome. Computed-axial tomography of the abdomen demonstrated an expansion of the left adrenal. In apparent contrast with these findings, adrenal scintigraphy demonstrated radiocholesterol uptake also by the right gland. At surgery, the left adrenal was found to be hard and enlarged and was excised, while the right gland was found of normal appearance and left in place. Histologic examination of the excised gland demonstrated nodular hyperplasia. Early after surgery, plasma cortisol returned to normal values with a normal circadian rhythm and complete inhibition by low dose dexamethasone; the response of plasma cortisol to ACTH was normal. The patient represents a rare case of unilateral adrenal nodular hyperplasia. Radiocholesterol uptake by the contralateral gland and early recovery from adrenal atrophy after surgery are exceptional findings and suggest incomplete inhibition of endogenous ACTH.

Gonadotropin releasing hormone elicits abnormal hormone responses in schizophrenia

We studied the non-specific responses of GH and PRL to gonadotropin releasing hormone (GnRH) in eleven male patients aged 18-30 in whom a diagnosis of acute schizophrenia was made according to Crows criteria. GnRH administration was followed by a significant increase in plasma GH in five patients; plasma PRL increased in two patients. The two prolactin responders were also GH responders. Non-specific GH response was confirmed on repeated testing in two patients in whom GnRH stimulation was performed twice. During saline control, non-specific hormone responses were not observed. The abnormal hormone responses observed in acute schizophrenia are probably due to the disordered monoamine regulation characteristic of this condition.