Browse

You are looking at 1 - 9 of 9 items for :

  • Oestradiol (E2) x
Clear All
Open access

Isabella Lupi, Alessandro Brancatella, Mirco Cosottini, Nicola Viola, Giulia Lanzolla, Daniele Sgrò, Giulia Di Dalmazi, Francesco Latrofa, Patrizio Caturegli and Claudio Marcocci

Summary

Programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen 4/B7 (CTLA-4/B7) pathways are key regulators in T-cell activation and tolerance. Nivolumab, pembrolizumab (PD-1 inhibitors), atezolizumab (PD-L1 inhibitor) and ipilimumab (CTLA-4 inhibitor) are monoclonal antibodies approved for treatment of several advanced cancers. Immune checkpoint inhibitors (ICIs)-related hypophysitis is described more frequently in patients treated with anti-CTLA-4; however, recent studies reported an increasing prevalence of anti-PD-1/PD-L1-induced hypophysitis which also exhibits slightly different clinical features. We report our experience on hypophysitis induced by anti-PD-1/anti-PD-L1 treatment. We present four cases, diagnosed in the past 12 months, of hypophysitis occurring in two patients receiving anti-PD-1, in one patient receiving anti-PD-1 and anti-CTLA-4 combined therapy and in one patient receiving anti-PD-L1. In this case series, timing, clinical presentation and association with other immune-related adverse events appeared to be extremely variable; central hypoadrenalism and hyponatremia were constantly detected although sellar magnetic resonance imaging did not reveal specific signs of pituitary inflammation. These differences highlight the complexity of ICI-related hypophysitis and the existence of different mechanisms of action leading to heterogeneity of clinical presentation in patients receiving immunotherapy.

Learning points:

  • PD-1/PD-L1 blockade can induce hypophysitis with a different clinical presentation when compared to CTLA-4 blockade.
  • Diagnosis of PD-1/PD-L1 induced hypophysitis is mainly made on clinical grounds and sellar MRI does not show radiological abnormalities.
  • Hyponatremia due to acute secondary adrenal insufficiency is often the principal sign of PD-1/PD-L1-induced hypophysitis and can be masked by other symptoms due to oncologic disease.
  • PD-1/PD-L1-induced hypophysitis can present as an isolated manifestation of irAEs or be in association with other autoimmune diseases
Open access

E Bahaeldein and M J Brassill

Summary

Postmenopausal hyperandrogenism is a relatively rare diagnosis resulting from excess androgen production from the adrenals or ovaries. The exclusion of malignant causes is a priority. Laboratory tests and imaging are utilised to help differentiate the source of excess androgens. We report two cases of postmenopausal hyperandrogenism in women aged 75 and 67 years. Both cases presented with clinical features suggestive of hyperandrogenism which had developed gradually over the previous 2 years. Laboratory investigations confirmed a significant elevation in their serum testosterone levels. In both cases, imaging did not reveal any abnormality of the adrenals or ovaries. To help differentiate an adrenal vs ovarian source a single-dose GnRH analogue was given with measurement of testosterone and gonadotrophin levels pre and post. The reduction in gonadotrophins achieved by the GnRH analogue resulted in suppression of testosterone levels which suggested an ovarian source. Both patients proceeded to bilateral oophorectomy. Histology revealed a benign hilus cell tumour in one case and a benign Leydig cell tumour in the other.

Learning points:

  • A key part of the work-up of postmenopausal hyperandrogenism is to differentiate between an adrenal or an ovarian source of excess androgens;
  • Imaging may not identify small ovarian tumours or hyperthecosis and may also identify incidental adrenal masses which are non-functioning;
  • Current guidelines suggest ovarian and adrenal venous sampling when imaging is inconclusive but this requires technical expertise and has a high failure rate;
  • GnRH analogue use can successfully confirm ovarian source and should be considered as a diagnostic tool in this setting.
Open access

W K M G Amarawardena, K D Liyanarachchi, J D C Newell-Price, R J M Ross, D Iacovazzo and M Debono

Summary

The granulation pattern of somatotroph adenomas is well known to be associated with differing clinical and biochemical characteristics, and it has been shown that sparsely granulated tumours respond poorly to commonly used somatostatin receptor ligands (SRLs). We report a challenging case of acromegaly with a sparsely granulated tumour resistant to multiple modalities of treatment, ultimately achieving biochemical control with pasireotide. A 26-year-old lady presented with classical features of acromegaly, which was confirmed by an oral glucose tolerance test. Insulin-like growth factor 1 (IGF1) was 1710 µg/L (103–310 µg/L) and mean growth hormone (GH) was >600 U/L. MRI scan showed a 4 cm pituitary macroadenoma with suprasellar extension and right-sided cavernous sinus invasion. She underwent trans-sphenoidal pituitary surgery. Histology displayed moderate amounts of sparsely granular eosinophilic cytoplasm, staining only for GH. Postoperative investigations showed uncontrolled disease (IGF1:1474 µg/L, mean GH:228 U/L) and residual tumour in the cavernous sinus. She received external beam fractionated radiation. Over the years, she received octreotide LAR (up to 30 mg), lanreotide (up to 120 mg) two weekly, cabergoline, pegvisomant and stereotactic radiosurgery to no avail. Only pegvisomant resulted in an element of disease control; however, this had to be stopped due to abnormal liver function tests. Fifteen years after the diagnosis, she was started on pasireotide 40 mg monthly. Within a month, her IGF1 dropped and has remained within the normal range (103–310 µg/L). Pasireotide has been well tolerated, and there has been significant clinical improvement. Somatostatin receptor subtyping revealed a positivity score of two for both sst5 and sst2a subtypes.

Learning points:

  • Age, size of the tumour, GH levels on presentation, histopathological type and the somatostatin receptor status of the tumour in acromegaly should be reviewed in patients who poorly respond to first-generation somatostatin receptor ligands.
  • Tumours that respond poorly to first-generation somatostatin receptor ligands, especially sparsely granulated somatotroph adenomas, can respond to pasireotide and treatment should be considered early in the management of resistant tumours.
  • Patients with membranous expression of sst5 are likely to be more responsive to pasireotide.
Open access

Ana Marina Moreira and Poli Mara Spritzer

Summary

Primary ovarian insufficiency (POI) is the condition of intermittent or permanent gonadal insufficiency that occurs in women before the age of 40. We describe three cases of POI referred to the outpatient endocrinology clinic of a university hospital. The three patients met diagnostic criteria for POI and were managed by specific approaches tailored to individualized goals. In the first case, the main concern was fertility and the reproductive prognosis. The second patient was a carrier of a common genetic cause of POI: premutation of the FMR1 gene. The third case was a patient diagnosed with a POI and established osteoporosis, a common complication of estrogen deprivation. This study reports the treatment and follow-up of these cases, with an emphasis on relevant aspects of individualized management, alongside a brief literature review.

Learning points

  • A diagnosis of POI should be considered in patients presenting with amenorrhea or irregular menses and high serum follicle-stimulating hormone (FSH) levels before age 40 years.
  • Patients with POI without an established cause, especially in familial cases, should be tested for FMR1 mutations.
  • Estrogen/progestin replacement therapy is indicated since diagnosis until at least the estimated age of menopause, and is the cornerstone for maintaining the good health of breast and urogenital tract and for primary or secondary osteoporosis prevention in POI.
  • Fertility should be managed through an individualized approach based on patient possibilities, such as egg or embryo donation and ovarian cryopreservation; pregnancy can occur spontaneously in a minority of cases.
  • Women with POI should be carefully monitored for cardiovascular risk factors.

Open access

Jeremy M W Kirk, Nalin Wickramasuriya and Nicholas J Shaw

Summary

Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of administration, in the UK oral ethinyl estradiol and the low-dose oral contraceptive pill are commonly used as hormone replacement therapy for practical reasons. We present five peripubertal girls (aged 12.5–14.9 years) with hypogonadism (two with primary hypogonadism due to Turner syndrome and three with central (secondary) hypogonadism as part of multiple pituitary hormone deficiency) who for a variety of reasons have received milligram doses of estradiol (E2) in error for between 6 weeks and 6 months, instead of the expected microgram doses of ethinyl estradiol. Although there are no direct comparisons in peripubertal girls between synthetic and natural estrogens, all girls had vaginal bleeding whilst receiving the milligram doses and have ended up with reduced final heights, below the 9th centile in 1 and below the 2nd centile in 4. Whilst reduction in final height may be part of the underlying condition (especially in Turner syndrome) the two girls with height predictions performed prior to receiving the estrogen overdose have not achieved their predicted height. Estrogen is one of the few drugs which is available in both milligram and microgram formulations. Clinicians need to be alert to the possibility of patients receiving the wrong formulation and dosage in error.

Learning points

  • Girls with primary and secondary gonadal failure require assistance with pubertal induction.
  • Although several different formulations and route of administration are available, for practical reasons, the majority of girls in the UK receive oral ethinyl estradiol.
  • Estrogen preparations are available in both milligram and microgram formulations, with potential for receiving the wrong dose.
  • Girls receiving milligram rather than microgram preparations all had vaginal bleeding and a short final height.

Open access

Nicole Maison, Esther Korpershoek, Graeme Eisenhofer, Mercedes Robledo, Ronald de Krijger and Felix Beuschlein

Summary

Pheochromocytomas (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors arising from chromaffin cells of the neural crest. Mutations in the RET-proto-oncogene are associated with sporadic pheochromocytoma, familial or sporadic medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia type 2. In the past, only few cases of pigmented PCCs, PGLs, and one case of pigmented MTC have been reported in the literature. Herein, we present the case of a 77-year old woman with a history of Tako-tsubo-cardiomyopathy and laboratory, as well as radiological, high suspicion of pheochromocytoma, who underwent left-sided adrenalectomy. The 3 cm tumor, which was located on the upper pole of the left adrenal, appeared highly pigmented with dark red to black color. Histologic examinations revealed highly pleomorphic cells with bizarre, huge hyperchromatic nuclei, that immunohistochemically were positive for chromogranin A and synaptophysin, focally positive for HMB45 and negative for melan A. These clinical and pathological features led to the diagnosis of the rare variant of a melanotic ‘black’ pheochromocytoma. In our case a somatic RET mutation in exon 16 (RET c.2753T>C, p.Met918Thy) was detected by targeted next generation sequencing. In summary, this case represents a rare variant of catecholamine-producing tumor with distinct histological features. A potential relationship between the phenotype, the cellular origin and the genetic alterations is discussed.

Learning points

  • Pheochromocytoma is a rare neuroendocrine tumor.
  • Pigmentation is seen in several types of tumors arising from the neural crest. The macroscopic black aspect can mislead to the diagnosis of a metastasis deriving from a malignant melanoma.
  • RET mutation are seen in catecholamine and non-catecholamine producing tumors of the same cellular origin.

Open access

W C Candy Sze, Joe McQuillan, P Nicholas Plowman, Niall MacDougall, Philip Blackburn, H Ian Sabin, Nadeem Ali and William M Drake

Summary

We report three patients who developed symptoms and signs of ocular neuromyotonia (ONM) 3–6 months after receiving gamma knife radiosurgery (GKS) for functioning pituitary tumours. All three patients were complex, requiring multi-modality therapy and all had received prior external irradiation to the sellar region. Although direct causality cannot be attributed, the timing of the development of the symptoms would suggest that the GKS played a contributory role in the development of this rare problem, which we suggest clinicians should be aware of as a potential complication.

Learning points

  • GKS can cause ONM, presenting as intermittent diplopia.
  • ONM can occur quite rapidly after treatment with GKS.
  • Treatment with carbamazepine is effective and improve patient's quality of life.

Open access

Sunita M C De Sousa, Peter Earls and Ann I McCormack

Summary

Pituitary hyperplasia (PH) occurs in heterogeneous settings and remains under-recognised. Increased awareness of this condition and its natural history should circumvent unnecessary trans-sphenoidal surgery. We performed an observational case series of patients referred to a single endocrinologist over a 3-year period. Four young women were identified with PH manifesting as diffuse, symmetrical pituitary enlargement near or touching the optic apparatus on MRI. The first woman presented with primary hypothyroidism and likely had thyrotroph hyperplasia given prompt resolution with thyroxine. The second and third women were diagnosed with pathological gonadotroph hyperplasia due to primary gonadal insufficiency, with histopathological confirmation including gonadal-deficiency cells in the third case where surgery could have been avoided. The fourth woman likely had idiopathic PH, though she had concomitant polycystic ovary syndrome which is a debated cause of PH. Patients suspected of PH should undergo comprehensive hormonal, radiological and sometimes ophthalmological evaluation. This is best conducted by a specialised multidisciplinary team with preference for treatment of underlying conditions and close monitoring over surgical intervention.

Learning points

  • Normal pituitary dimensions are influenced by age and gender with the greatest pituitary heights seen in young adults and perimenopausal women.
  • Pituitary enlargement may be seen in the settings of pregnancy, end-organ insufficiency with loss of negative feedback, and excess trophic hormone from the hypothalamus or neuroendocrine tumours.
  • PH may be caused or exacerbated by medications including oestrogen, GNRH analogues and antipsychotics.
  • Management involves identification of cases of idiopathic PH suitable for simple surveillance and reversal of pathological or iatrogenic causes where they exist.
  • Surgery should be avoided in PH as it rarely progresses.

Open access

Gabriela Alejandra Sosa, Soledad Bell, Silvia Beatriz Christiansen, Marcelo Pietrani, Mariela Glerean, Monica Loto, Soledad Lovazzano, Antonio Carrizo, Pablo Ajler and Patricia Fainstein Day

Summary

IgG4-related hypophysitis is a recently described entity belonging to the group of IgG4-related diseases. Many other organs can also be affected, and it is more common in older men. To date, 32 cases of IgG4-related hypophysitis have been reported in the literature, 11 of which included confirmatory tissue biopsy and the majority affecting multiple organs. The aim of this report is to present two cases of biopsy-proven IgG4-related hypophysitis occurring in two young female patients with no evidence of involvement of other organs at the time of diagnosis.

Learning points

  • IgG4-related hypophysitis belongs to the group of IgG4-related diseases, and is a fibro-inflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells and storiform fibrosis.
  • It is more common in older men, but young women may also present this type of hypophysitis.
  • Although involvement of other organs is frequent, isolated pituitary disease is possible.
  • Frequent clinical manifestations include anterior hypopituitarism and/or diabetes insipidus.
  • The diagnosis may be confirmed with any of the following criteria: a pituitary biopsy with lymphoplasmacytic infiltrates, with more than ten IgG4-positive cells; a sellar mass and/or thickened pituitary stalk and a biopsy-proven involvement of another organ; a sellar mass and/or thickened pituitary stalk and IgG4 serum levels >140 mg/dl and sellar mass reduction and symptom improvement after corticosteroid treatment.
  • Glucocorticoids are recommended as first-line therapy.