Diagnosis and Treatment > Investigation > GNRH stimulation
You are looking at 1 - 4 of 4 items
Search for other papers by Philip D Oddie in
Google Scholar
PubMed
Search for other papers by Benjamin B Albert in
Google Scholar
PubMed
Starship Children’s Health, Auckland District Health Board, Auckland, New Zealand
Search for other papers by Paul L Hofman in
Google Scholar
PubMed
Starship Children’s Health, Auckland District Health Board, Auckland, New Zealand
Search for other papers by Craig Jefferies in
Google Scholar
PubMed
Search for other papers by Stephen Laughton in
Google Scholar
PubMed
Search for other papers by Philippa J Carter in
Google Scholar
PubMed
Summary
Adrenocortical carcinoma (ACC) during childhood is a rare malignant tumor that frequently results in glucocorticoid and/or androgen excess. When there are signs of microscopic or macroscopic residual disease, adjuvant therapy is recommended with mitotane, an adrenolytic and cytotoxic drug. In addition to the anticipated side effect of adrenal insufficiency, mitotane is known to cause gynecomastia and hypothyroidism in adults. It has never been reported to cause precocious puberty. A 4-year-old girl presented with a 6-week history of virilization and elevated androgen levels and 1-year advancement in bone age. Imaging revealed a right adrenal mass, which was subsequently surgically excised. Histology revealed ACC with multiple unfavorable features, including high mitotic index, capsular invasion and atypical mitoses. Adjuvant chemotherapy was started with mitotane, cisplatin, etoposide and doxorubicin. She experienced severe gastrointestinal side effects and symptomatic adrenal insufficiency, which occurred despite physiological-dose corticosteroid replacement. She also developed hypothyroidism that responded to treatment with levothyroxine and peripheral precocious puberty (PPP) with progressive breast development and rapidly advancing bone age. Five months after discontinuing mitotane, her adrenal insufficiency persisted and she developed secondary central precocious puberty (CPP). This case demonstrates the diverse endocrine complications associated with mitotane therapy, which contrast with the presentation of ACC itself. It also provides the first evidence that the known estrogenic effect of mitotane can manifest as PPP.
Learning points:
-
Adrenocortical carcinoma is an important differential diagnosis for virilization in young children
-
Mitotane is a chemotherapeutic agent that is used to treat adrenocortical carcinoma and causes adrenal necrosis
-
Mitotane is an endocrine disruptor. In addition to the intended effect of adrenal insufficiency, it can cause hypothyroidism, with gynecomastia also reported in adults.
-
Patients taking mitotane require very high doses of hydrocortisone replacement therapy because mitotane interferes with steroid metabolism. This effect persists after mitotane therapy is completed
-
In our case, mitotane caused peripheral precocious puberty, possibly through its estrogenic effect.
Search for other papers by Shunsuke Funazaki in
Google Scholar
PubMed
Search for other papers by Hodaka Yamada in
Google Scholar
PubMed
Search for other papers by Kazuo Hara in
Google Scholar
PubMed
Division of Endocrinology and Metabolism Division of Endocrinology and Metabolism, International University of Health and Welfare Hospital, Tochigi, Japan
Search for other papers by San-e Ishikawa in
Google Scholar
PubMed
Summary
Lymphocytic hypophysitis (LyH) has been known to be associated with pregnancy. We herein report the case of a 33-year-old woman who underwent vaginal delivery without massive bleeding at 40 weeks of gestation. Because of the presence of headache and terrible fatigue after childbirth, she visited our hospital. Severe hyponatremia (Na, 118 mEq/L) and visual field abnormality was noted upon examination. MRI revealed pituitary enlargement with a swollen pituitary stalk, albeit at low signal intensity. Basal pituitary hormone levels were all reduced and remained low after exogenous administration of hypothalamic-releasing hormones. She was diagnosed with LyH and was started on prednisolone 60 mg/day. A month later, her pituitary function had gradually improved together with a decrease in pituitary enlargement and recovery of her visual field. The dose of prednisolone was gradually reduced and finally withdrawn 27 months later. After prednisolone withdrawal, her pituitary function remained normal despite the absence of any hormonal replacement. A year later, she became pregnant without medication and delivered a second baby without LyH recurrence. Thereafter, her pituitary function has been normal for more than 5 years. Two valuable observations can be highlighted from the case. First, the patient completely recovered from LyH through prompt prednisolone therapy during its initial phase and had almost normal pituitary function. Second, after recovery from LyH, she was able to undergo spontaneous pregnancy and deliver a baby. We believe that reporting incidences of spontaneous pregnancy after complete normalization of pituitary function in patients with LyH is of great significance.
Learning points:
-
Females are more affected by LyH than males given its strong association with pregnancy.
-
LyH possesses characteristic findings on pituitary MRI.
-
Glucocorticoid therapy for LyH has been recommended as an effective treatment.
-
A history of previous pregnancies does not increase the risk of developing AH in subsequent pregnancies.
-
Early induction of high-dose prednisolone was therapeutically effective in treating LyH.
Search for other papers by Bronwen E Warner in
Google Scholar
PubMed
Search for other papers by Carol D Inward in
Google Scholar
PubMed
NIHR Biomedical Research Unit in Nutrition, Diet & Lifestyle, University Hospitals Bristol NHS Foundation Trust, Education Centre, Bristol, UK
Search for other papers by Christine P Burren in
Google Scholar
PubMed
Summary
This case, presenting with bilateral impalpable testes, illustrates the relevance of a broad differential disorders of sex development case management. It provides new insights on hypothalamic–pituitary–gonadal (HPG) axis and testicular function abnormalities in the multisystem disorder of Lowe syndrome. Lowe syndrome, also known as oculocerebrorenal syndrome, is a rare disorder characterised by eye abnormalities, central nervous system involvement and proximal renal tubular acidosis. There are a handful of reports of pubertal delay, infertility and cryptorchidism in Lowe syndrome. Biochemistry aged 72 h: testosterone 6.4 nmol/L, LH <0.5 IU/L and FSH <0.5 IU/L. Gonadotropin-releasing hormone stimulation test identified significantly raised baseline LH = 45.4 IU/L (contrasts with earlier undetectable LH), with a 20% increase on stimulation, while baseline FSH = 4.3 IU/L with no increase on stimulation. Day 14 HCG stimulation test produced an acceptable 50% increase in testosterone. The constellation of further abnormalities suggested Lowe syndrome: hypotonia, bilateral cataracts (surgical extraction and intraocular lens implantation) and renal tubular acidosis (microscopic haematuria, hypercalciuria, proteinuria, generalised aminoaciduria, hypophosphataemia and metabolic acidosis). DNA sequencing identified de novo hemizygous frameshift mutation OCRL c.2409_2410delCT in exon 22. Interpretation of initial and repeat GnRH and HCG testing indicates the likelihood of testicular failure. Partial testicular descent occurred but left orchidopexy was required. Improving long-term gonadal function in Lowe syndrome assumes increased importance for current cohorts as advances in renal replacement therapy have greatly improved life expectancy. Noting HPG axis abnormalities in Lowe syndrome in infancy can identify cases requiring increased surveillance of pubertal progress for earlier detection and management.
Learning points:
-
Clinical endocrine problems in Lowe syndrome has been reported, but has focused on abnormalities in adolescence and young adulthood: pubertal delay and infertility.
-
We present an infant with isolated LH elevation at baseline and on GnRH stimulation testing who also had bilateral impalpable testes.
-
Early testing of the HPG axis in patients with Lowe syndrome may help predict gonadal abnormalities from a younger age, which will enhance the overall case management into adolescence.
Search for other papers by S Vimalesvaran in
Google Scholar
PubMed
Search for other papers by S Narayanaswamy in
Google Scholar
PubMed
Search for other papers by L Yang in
Google Scholar
PubMed
Search for other papers by J K Prague in
Google Scholar
PubMed
Search for other papers by A Buckley in
Google Scholar
PubMed
Search for other papers by A D Miras in
Google Scholar
PubMed
Search for other papers by S Franks in
Google Scholar
PubMed
Search for other papers by K Meeran in
Google Scholar
PubMed
Search for other papers by W S Dhillo in
Google Scholar
PubMed
Summary
Primary amenorrhoea is defined as the failure to commence menstruation by the age of 15 years, in the presence of normal secondary sexual development. The potential causes of primary amenorrhoea extend from structural to chromosomal abnormalities. Polycystic ovarian syndrome (PCOS) is a common cause of secondary amenorrhoea but an uncommon cause of primary amenorrhoea. An early and prompt diagnosis of PCOS is important, as up to 30% of these women are predisposed to glucose intolerance and obesity, with the subgroup of women presenting with primary amenorrhoea and PCOS displaying a higher incidence of metabolic dysfunction. We describe a case of an 18-year-old female presenting with primary amenorrhoea of unknown aetiology. Although initial investigations did not demonstrate clinical or biochemical hyperandrogenism or any radiological evidence of polycystic ovaries, a raised luteinising hormone (LH) suggested a diagnosis of PCOS. If PCOS was the correct diagnosis, then one would expect intact hypothalamic GnRH and pituitary gonadotropin release. We used the novel hormone kisspeptin to confirm intact hypothalamic GnRH release and a GnRH stimulation test to confirm intact pituitary gonadotroph function. This case highlights that kisspeptin is a potential unique tool to test GnRH function in patients presenting with reproductive disorders.
Learning points:
-
Polycystic ovarian syndrome (PCOS) can present with primary amenorrhoea, and therefore, should be considered in the differential diagnosis.
-
PCOS is a heterogeneous condition that may present in lean women with few or absent signs of hyperandrogenism.
-
GnRH stimulation tests are useful in evaluating pituitary function; however, to date, we do not have a viable test of GnRH function. Kisspeptin has the potential to form a novel diagnostic tool for assessing hypothalamic GnRH function by monitoring gonadotropin response as a surrogate marker of GnRH release.
-
Confirmation of intact GnRH function helps consolidate a diagnosis in primary amenorrhoea and gives an indication of future fertility.