Oana Ruxandra Cotta

Prolactin in obese children: a bridge between inflammation and metabolic-endocrine dysfunction

Adipocytes, regulated by insulin, represent the major peripheral source of prolactin (PRL), which play a pivotal role in energy balance, acting on adipogenesis and lipolysis. The aim of this study was to investigate whether PRL was associated with obesity‐related inflammatory status and metabolic parameters. The diagnostic and prognostic role of PRL for metabolic syndrome (MS) was assessed. The effects of short‐term lifestyle therapy on PRL levels were evaluated.

Lymphocytic Hypophysitis: Differential Diagnosis and Effects of High-Dose Pulse Steroids, Followed by Azathioprine, on the Pituitary Mass and Endocrine Abnormalities — Report of a Case and Literature Review

We report on a man with a progressively increasing pituitary mass, as demonstrated by MRI. It produced neurological and ophthalmological symptoms, and, ultimately, hypopituitarism. MRI also showed enlargement of the pituitary stalk and a dural tail phenomenon. An increased titer of antipituitary antibodies (1:16) was detected in the serum. Pituitary biopsy showed autoimmune hypophysitis (AH). Neither methylprednisolone pulse therapy nor a subsequent treatment with azathioprine were successful in recovering pituitary function, or in inducing a significant reduction of the pituitary mass after an initial, transient clinical and neuroradiological improvement. Anterior pituitary function evaluation revealed persistent hypopituitarism. AH is a relatively rare condition, particularly in males, but it represents an emerging entity in the diagnostic management of pituitary masses. This case shows that response to appropriate therapy for hypophysitis may not be very favorable and confirms that diagnostic management of nonsecreting pituitary masses can be a challenge. Clinical, imaging, and laboratory findings are useful for suggesting the diagnosis, but pituitary biopsy may be necessary to confirm it.

Increased frequency of the rs2066853 variant of aryl hydrocarbon receptor gene in patients with acromegaly

Aryl hydrocarbon receptor (AHR) pathway has a key role in cellular detoxification mechanisms and seems implicated in tumorigenesis. Moreover, polymorphisms and mutations of AHR gene have been associated with several human and animal tumours. Although AHR has been found differently expressed in pituitary adenomas, AHR gene mutation status has never been investigated in acromegalic patients.

Role of pituitary dysfunction on cardiovascular risk in primary empty sella patients

Primary empty sella (PES) is a frequent anatomical condition rarely causing pituitary dysfunction. We assessed cardiovascular risk in a cohort of PES patients referred to Endocrine Units.

Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism

Mitotane, a steroidogenesis inhibitor with adrenolytic properties used to treat adrenocortical cancer (ACC), can affect thyroid function. A reduction of FT4 levels with normal FT3 and TSH has been described in these patients. Using an in vitro murine model, the secretory capacity of thyrotrophic cells has been shown to be inhibited by mitotane.

How to diagnose and manage Cushing’s disease during pregnancy, when hypercortisolism is mild?

Diagnosis of mild Cushing’s disease (CD) can be difficult in pregnant women, because its clinical and biochemical features can be erroneously interpreted as consequence of the gestation. Corticotropin releasing hormone (CRH) and desmopressin (DDAVP) tests are currently used to confirm CD, but data concerning adrenocorticotropic hormone (ACTH) response during pregnancy are lacking. A woman with mild cushingoid features was evaluated during the first trimester of gestation. Serum cortisol was normal at morning, but increased at midnight and incompletely suppressed by 1-mg dexamethasone overnight administration. Also 24-h urinary free cortisol levels were mildly elevated. She delivered vaginally a healthy newborn at the 39th week of an uneventful pregnancy. After delivery, an ACTH-secreting microadenoma was surgically removed. During the first trimester of gestation and after delivery, human CRH (h-CRH) and DDAVP-stimulated ACTH peaks were higher than those measured in 22 healthy premenopausal women. While the ACTH/h-CRH peak was intermediate between those measured in the healthy women and in 9 CD female patients, ACTH/DDAVP peak was in the range of CD patients and dramatically higher than those of healthy women. However, ACTH increase after h-CRH was significantly higher after delivery than during gestation (p < 0.003), while ACTH responses to DDAVP were similar. In pregnant women with mild cushingoid features, h-CRH and DDAVP tests are useful to confirm the diagnosis of CD. Mild hypercortisolism can be well tolerated, but cardiovascular and metabolic parameters should be monitored carefully.

Cardiovascular outcomes and conventional risk factors in non-diabetic adult patients with GH deficiency: A long-term retrospective cohort study

PURPOSE To investigate the association between cardiovascular (CV) risk factors and cumulative CV events in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT). METHODS 53 non-diabetic adult GHD patients, aged 45.4±14.3years, 31 females, with a median follow up of 140months, were divided into two groups based on the presence (group A) or absence (group B) of systemic hypertension. Tertiles of age and LDL-cholesterol were considered as further potential prognosticators. Cumulative CV event rates were recorded and analyzed by Kaplan-Mayer method. Differences between patients with and without events were also evaluated. RESULTS Seventeen patients (32%) entered the group A and 36 (68%) the group B. A composite of fatal and non-fatal CV events occurred in 22.6% of patients, 47.1% in group A and 11% in group B (p=0.01), CV deaths in 3 patients (5.7%; annual death rate 0.49%), 2 of whom were in group A. At Kaplan-Mayer analysis, hypertension and age>55years were major prognosticators. The odds ratio was 7.1 (95% CI: 1.74-29.12, p<0.003) and 6.2 (95% CI: 1.54-25.04, p<0.006), respectively. LDL-cholesterol showed borderline statistical significance. Patients with CV events also had high prevalence of left ventricular hypertrophy, left atrial enlargement and subclinical systolic dysfunction. CONCLUSIONS In this study, outcomes were mainly related to hypertension and age (partially to LDL-cholesterol), confirming that management of GHD patients must be inclusive of treatment of conventional risk factors, being as important as GHRT. Optimal blood pressure control is crucial when a target organ damage is present and in patients older than 55years.

Course of pregnancies in women with Cushing's disease treated by gamma-knife

Data concerning pregnancy in women with Cushing’s disease treated by gamma-knife (GK) are scanty. We present and discuss the course and outcome of five pregnancies in two women with Cushing’s disease (CD), the first of whom was treated only by GK, and the second one treated by surgery, GK and ketoconazole. In the first patient, pregnancy was uneventful and full-term. During gestation, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were steady, and always in the normal range for healthy non-pregnant individuals. The newborn was healthy and normal-weight. In the second woman, two pregnancies, occurring 3 years after GK and few months after ketoconazole withdrawal, were interrupted by spontaneous abortion or placental disruption despite normal cortisol levels. This patient became again pregnant 3 years later and delivered vaginally a healthy full-term infant. Seven months after the delivery, the patient became pregnant again and at the 39th week of gestation delivered vaginally a healthy male. Hypoprolactinemia and/or central hypothyroidism occurred in both cases. In women with CD treated by GK, pregnancy can occur. However, pregnancy is at risk even when ACTH and cortisol levels are normalized by treatment. After GK, evaluation of pituitary function is mandatory due to the risk of hypopituitarism.