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Fulltext Pachydermoperiostosis: a rare mimicker of acromegaly

Abdullah NRA, Jason WLC, Nasruddin AB

Endocrinol Diabetes Metab Case Rep, 2017;2017.
PMID: 28567291 DOI: 10.1530/EDM-17-0029

Pachydermoperiostosis is a very rare osteoarthrodermopathic disorder whose clinical and radiographic presentations may mimic those of acromegaly. In the evaluation of patients with acromegaloid appearances, pachydermoperiostosis should be considered as a differential diagnosis. In this article, we report a 17-year-old boy who presented with 2-year history of acral enlargement and facial appearance changes associated with joint pain and excessive sweating. He had been investigated extensively for acromegaly, and the final diagnosis was pachydermoperiostosis.
LEARNING POINTS: There is a broad range of differential diagnosis for acromegaloid features such as acromegaly, pseudoacromegaly with severe insulin resistance, Marfan's syndrome, McCune-Albright and a rare condition called pachydermoperiostosis.Once a patient is suspected to have acromegaly, the first step is biochemical testing to confirm the clinical diagnosis, followed by radiologic testing to determine the cause of the excess growth hormone (GH) secretion. The cause is a somatotroph adenoma of the pituitary in over 95 percent of cases.The first step is measurement of a serum insulin-like growth factor 1 (IGF1). A normal serum IGF1 concentration is strong evidence that the patient does not have acromegaly.If the serum IGF1 concentration is high (or equivocal), serum GH should be measured after oral glucose administration. Inadequate suppression of GH after a glucose load confirms the diagnosis of acromegaly.Once the presence of excess GH secretion is confirmed, the next step is pituitary magnetic resonance imaging (MRI).Atypical presentation warrants revision of the diagnosis. This patient presented with clubbing with no gigantism, which is expected in adolescent acromegalics as the growth spurt and epiphyseal plate closure have not taken place yet.

Matched MeSH terms: Pituitary Gland
Fulltext Effects of an indigenous contraceptive herbal formulation on gonadotrophs of the pituitary gland of the rat

Islam MN, Sulaiman SA, Kapitonova MY, Jamallullail SM

Malays J Med Sci, 2007 Jan;14(1):23-7.
PMID: 22593648

An indigenous contraceptive herbal formulation consisting of a mixture of Lepidagathis longifolia, Palaquium sp and Phyllagathis rotundifolia is being used by the Temuan Aborigins of Malaysia. Although the previous studies demonstrated that this contraceptive herbal formulation causes anovulatory estrous cycle, altered circulating hormone levels and fetal resorption in rats, but the effects of this formulation on the gonadotrphs of the pituitary gland are yet to be evaluated. The present study was designed to observe the morphometric changes of the gonadotrophs and the plasma concentrations of follicle stimulating hormone and leutinizing hormone. Thirty five Sprague-Dawley adult female rats were randomly divided into 5 groups. Experimental animals were given a combined herbal extract or individual herbal extract at a dose of 540 mg/kg/day subcutaneously for 7 days. Immunostained gonadotrophs were studied by using image analyzer. FSH and LH serum concentrations were determined using RIA. The FSH and LH concentrations were low in animals that received combined herbal extract (p<0.01). FSH concentration was noted to be significantly low in animals that received P. rotundifolia (p<0.05). The mean cell area and cell density of gonadotrophs of animals that received combined herbal extract were significantly low compared to control group (p<0.05). It was concluded that the herbal extracts do suppress the production of gonaotrophins along with the demonstrable suppresive effect on the FSH cells.

Matched MeSH terms: Pituitary Gland
Fulltext Osmoregulation requires brain expression of the renal Na-K-2Cl cotransporter NKCC2

Konopacka A, Qiu J, Yao ST, Greenwood MP, Greenwood M, Lancaster T, et al.

J Neurosci, 2015 Apr 01;35(13):5144-55.
PMID: 25834041 DOI: 10.1523/JNEUROSCI.4121-14.2015

The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. The HNS controls osmotic stability through the synthesis and release of the neuropeptide hormone, arginine vasopressin (AVP). AVP travels through the bloodstream to the kidney, where it promotes water conservation. Knockdown of HNS NKCC2 elicited profound effects on fluid balance following ingestion of a high-salt solution-rats produced significantly more urine, concomitant with increases in fluid intake and plasma osmolality. Since NKCC2 is the molecular target of the loop diuretics bumetanide and furosemide, we asked about their effects on HNS function following disturbed water balance. Dehydration-evoked GABA-mediated excitation of AVP neurons was reversed by bumetanide, and furosemide blocked AVP release, both in vivo and in hypothalamic explants. Thus, NKCC2-dependent brain mechanisms that regulate osmotic stability are disrupted by loop diuretics in rats.

Matched MeSH terms: Pituitary Gland, Posterior/cytology; Pituitary Gland, Posterior/drug effects; Pituitary Gland, Posterior/metabolism*
Endonasal endoscopic repair of anterior skull-base fistulas: the Kuala Lumpur experience

Gendeh BS, Mazita A, Selladurai BM, Jegan T, Jeevanan J, Misiran K

J Laryngol Otol, 2005 Nov;119(11):866-74.
PMID: 16354338

The purpose of this retrospective study is to determine the pattern of cerebrospinal fluid (CSF) rhinorrhoea presenting to our tertiary referral centre in Kuala Lumpur and to assess the clinical outcomes of endonasal endoscopic surgery for repair of anterior skull base fistulas. Sixteen patients were treated between 1998 and 2004. The aetiology of the condition was spontaneous in seven and acquired in nine patients. In the acquired category, three patients had accidental trauma and this was iatrogenic in six patients (five post pituitary surgery), with one post endoscopic sinus surgery (ESS). Imaging included computed tomography (CT) scan and magnetic resonance imaging (MRI). Endoscopic repair is less suited for defects in the frontal sinuses with prominent lateral extension and defects greater than 1.5 cm in diameter involving the skull base. Fascia lata, middle turbinate mucosa, nasal perichondrium and ear fat ('bath plug') were the preferred repair materials in the anterior skull base, whereas fascia lata, cartilage and abdominal fat obliteration was preferentially used in the sphenoid leak repair. Intrathecal sodium flourescein helped to confirm the site of CSF fistula in 81.3 per cent of the patients. Ninety per cent of the patients who underwent 'bath plug' repair were successful. The overall success rate for a primary endoscopic procedure was 87.5 per cent, although in two cases a second endoscopic procedure was required for closure. In the majority of cases endoscopic repair was successful, and this avoids many of the complications associated with craniotomy, particularly in a young population. Therefore it is our preferred option, but an alternative procedure should be utilized should this prove necessary.

Matched MeSH terms: Pituitary Gland/surgery
Sexual maturation modulates expression of nuclear receptor types in laser-captured single cells of the cichlid (Oreochromis niloticus) pituitary

Kitahashi T, Ogawa S, Soga T, Sakuma Y, Parhar I

Endocrinology, 2007 Dec;148(12):5822-30.
PMID: 17823257

The role of steroid/thyroid hormones in the regulation of endocrine cells at the level of the pituitary has remained unclear. Therefore, using single-cell quantitative real-time PCR, we examined absolute amounts of transcripts for nuclear receptors [estrogen receptors (ERs) alpha, beta, and gamma; androgen receptors (ARs) a and b; glucocorticoid receptors (GRs) 1, 2a, and 2b; and thyroid hormone receptors (TRs) alpha1, alpha2, and beta] in pituitary cells of immature (IM) and mature (M) male tilapia, Oreochromis niloticus. In the two reproductive stages, ACTH cells expressed only ERbeta, whereas all other pituitary cell types expressed ERalpha + beta, and a subpopulation coexpressed ARa, ARb, GR1, GR2b, and TRbeta but lacked ERgamma, GR2a, TRalpha1, and TRalpha2. IM males had high percentages of LH cells (IM 46.0% vs. M 10.0%), GH cells (IM 23.3% vs. M 7.9%), and prolactin cells (IM 68.8% vs. M 6.0%) with ERbeta, and TSH cells (IM 19.2% vs. M 0.0%) and MSH cells (IM 25.6% vs. M 0.0%) with ERalpha + TRbeta. A high percentage of FSH cells in IM males expressed ERbeta (IM 46.9% vs. M 18.8%), and FSH cells in M males showed significantly high GR1 transcripts (IM 76.0 +/- 5.0 vs. M 195.0 +/- 10.7 copies per cell; P < 0.05), suggesting that FSH cells are regulated differently in the two reproductive stages. Coexpression of ERalpha + beta in high percentages of cells of the GH family (GH, IM 43.8% vs. M 14.3%; prolactin, IM 8.3% vs. M 59.7%; somatolactin, IM 22.2% vs. M 42.2%) suggests that the expression of both ERs is important for functionality. Thus, differential coexpression of genes for nuclear receptors in subpopulations of pituitary cell types suggests multiple steroid/thyroid hormone regulatory pathways at the level of the pituitary during the two reproductive stages.

Matched MeSH terms: Pituitary Gland/cytology; Pituitary Gland/metabolism*
Fulltext Rasd1, a small G protein with a big role in the hypothalamic response to neuronal activation

Greenwood MP, Greenwood M, Mecawi AS, Antunes-Rodrigues J, Paton JF, Murphy D

Mol Brain, 2016 Jan 07;9:1.
PMID: 26739966 DOI: 10.1186/s13041-015-0182-2

BACKGROUND: Rasd1 is a member of the Ras family of monomeric G proteins that was first identified as a dexamethasone inducible gene in the pituitary corticotroph cell line AtT20. Using microarrays we previously identified increased Rasd1 mRNA expression in the rat supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus in response to increased plasma osmolality provoked by fluid deprivation and salt loading. RASD1 has been shown to inhibit adenylyl cyclase activity in vitro resulting in the inhibition of the cAMP-PKA-CREB signaling pathway. Therefore, we tested the hypothesis that RASD1 may inhibit cAMP stimulated gene expression in the brain.
RESULTS: We show that Rasd1 is expressed in vasopressin neurons of the PVN and SON, within which mRNA levels are induced by hyperosmotic cues. Dexamethasone treatment of AtT20 cells decreased forskolin stimulation of c-Fos, Nr4a1 and phosphorylated CREB expression, effects that were mimicked by overexpression of Rasd1, and inhibited by knockdown of Rasd1. These effects were dependent upon isoprenylation, as both farnesyltransferase inhibitor FTI-277 and CAAX box deletion prevented Rasd1 inhibition of cAMP-induced gene expression. Injection of lentiviral vector into rat SON expressing Rasd1 diminished, whereas CAAX mutant increased, cAMP inducible genes in response to osmotic stress.
CONCLUSIONS: We have identified two mechanisms of Rasd1 induction in the hypothalamus, one by elevated glucocorticoids in response to stress, and one in response to increased plasma osmolality resulting from osmotic stress. We propose that the abundance of RASD1 in vasopressin expressing neurons, based on its inhibitory actions on CREB phosphorylation, is an important mechanism for controlling the transcriptional responses to stressors in both the PVN and SON. These effects likely occur through modulation of cAMP-PKA-CREB signaling pathway in the brain.

Matched MeSH terms: Pituitary Gland, Posterior/drug effects; Pituitary Gland, Posterior/metabolism