Search for other papers by Aishah Alhajeri in
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Summary
Menstrual cycle abnormalities are common in premenopausal females with Cushing’s syndrome, although the underlying mechanism is poorly understood. Signs and symptoms found in Cushing’s syndrome overlap with polycystic ovarian syndrome (PCOS). The patient is a 33-year-old female previously diagnosed by a gynecologist with PCOS and treated with oral contraceptive pills (OCPs) for 2 years. She then discontinued her OCPs without consulting a clinician, resulting in amenorrhea for 6 months, for which she presented. She also had symptoms of depression and anxiety but had no other signs and symptoms of Cushing’s syndrome, except a plethoric face. Initial lab work showed evidence of central hypogonadism (low luteinizing hormone, follicle-stimulating hormone, and estrogen), so a complete anterior pituitary hormone workup was done. Her thyroid-stimulating hormone was also low with a low free T4 level. Prolactin level was normal, but surprisingly, her AM cortisol level was high. The Cushing’s syndrome workup revealed non-suppressed cortisol after a 1 mg dexamethasone suppression test and positive 24-h urine cortisol with suppressed adrenocorticotrophic hormone. A CT scan of her adrenal glands revealed a left adrenal adenoma. She underwent a left adrenalectomy, after which her menstrual cycles became regular again, and pituitary function has recovered.
Learning points
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In Cushing's syndrome, female patients can have menstrual abnormalities due to the high cortisol levels, which can affect gonadotrophin levels.
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We encourage clinicians to include Cushing's syndrome in the differential diagnosis of patients with central hypogonadism.
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Rady Children’s Hospital, University of California, San Diego, California, USA
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Summary
A 6.6-year-old female presented to endocrinology with precocious puberty for evaluation and management. Workup was initiated, and a diagnosis of central precocious puberty was confirmed. A decision was made to initiate pubertal blockade using gonadotropin-releasing hormone agonist (GnRHa) therapy with depot leuprolide acetate injections every 3 months. The patient received the first depot leuprolide acetate injection in the right ventrogluteal area. Six hours following the injection, the patient was reported to be inconsolable in pain, which was localized to the right hip site of the earlier injection and associated with a refusal to ambulate. The pain and discomfort continued to progress over the next 24 h despite an alternating regimen of Tylenol and ibuprofen prompting admission to the emergency department. Vital signs demonstrated a low-grade fever and elevated C-reactive protein. An ultrasound of the right hip demonstrated fluid accumulation within the joint. Over the next week, the patient was unable to walk independently and required assistance for activities of daily living. By 2 weeks after the injection, the pain began to remit, and the patient resumed activities of daily living. Following consultation with allergy, a decision was made to continue GnRHa suppressive therapy with an alternative analog (Triptodur). The patient tolerated subsequent treatment without reaction.
Learning points
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Although gonadotropin-releasing hormone agonists (GnRHa) have a generally good safety profile, there is a history of both local and systemic hypersensitivity reactions associated with their use.
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Despite the long-acting formulation of depot leuprolide acetate, the systemic reaction in this case appears to be self-limited.
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Discontinuation of therapy or a change to an alternative formulation of GnRHa analog should be considered based on the need for therapy versus the potential risk of rechallenge.
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Search for other papers by Joanna Yuet-ling Tung in
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Summary
17α-hydroxylase deficiency (17α-OHD) is a rare form of congenital adrenal hyperplasia. We report the case of a teenage girl with 17α-OHD who presented with delayed puberty, hypergonadotropic hypogonadism and hypertension. We illustrate the clinical approach in workup, the subsequent management and monitoring of this rare condition.
Learning points
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17α-hydroxylase deficiency (17α-OHD) should be considered as a rare yet important differential diagnosis of girls with delayed puberty and elevated gonadotropins.
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Urine steroid profile, plasma aldosterone and renin levels should be assessed in adolescent girls with hypergonadotropic hypogonadism, after the exclusion of more common conditions, e.g. Turner syndrome.
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Inhibiting deoxycorticosterone (DOC) release by partial glucocorticoid replacement, counteracting DOC’s mineralocorticoid effects by antagonists (such as eplerenone or spironolactone) as well as sex hormone replacements constitute the major backbone in the management of 17α-OHD.
Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
School of Medicine, University of Western Australia, Nedlands, Western Australia, Australia
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Summary
A 33-year-old man with Kallmann syndrome had received pulsatile GnRH as an infant for the treatment of cryptorchidism. As an adult, his treatment for fertility with gonadotrophins was unusually rapid compared with expectations, with a total sperm count of 25 million after only 12 months of gonadotrophin therapy. We propose that pulsatile GnRH treatment as an infant induced minipuberty and facilitated his successful, rapid response to therapy. We also propose that identification of the absence of minipuberty in infants with clinical signs suggesting congenital hypogonadotrophic hypogonadism (CHH) is an opportunity for intervention with pulsatile GnRH yielding benefits for fertility decades later.
Learning points
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Absence of minipuberty in males with CHH results in low Sertoli cell numbers and delayed response to induction of spermatogenesis in adulthood.
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Presentation with 'red flags' for androgen deficiency including cryptorchidism at birth, with or without micropenis, should prompt screening for CHH and minipuberty by measurement of gonadotrophins and testosterone in the first 2 months after birth.
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Pulsatile GnRH therapy in patients with CHH, given prior to age of attainment of Sertoli cell maturation, can replicate the normal physiology of minipuberty, thereby priming the testis for future fertility.
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Summary
Kallmann syndrome (KS) is a genetically heterogeneous condition characterized by hypogonadotropic hypogonadism with coexisting anosmia or hyposmia along with potential other phenotypic abnormalities depending on the specific genetic mutation involved. Several genetic mutations have been described to cause KS. The ANOS1 (KAL1) gene is responsible for 8% of mutations causing KS. A 17-year-old male presented to our clinic with delayed puberty and hyposmia, along with a family history suggestive of hypogonadism in his maternal uncle. Genetic testing for KS revealed complete exon 3 deletion in the ANOS1 gene. To the best of our knowledge, this specific mutation has not been previously described in the literature.
Learning points
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Missense and frameshift mutations in the KAL1 or ANOS1 gene located in the X chromosome are responsible for 8% of all known genetic mutations of Kallmann syndrome.
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Exon 3 deletion is one of the ANOS1 gene is a novel mutation, not reported before.
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Targeted gene sequencing for hypogonadotropic hypogonadism can be employed based on the phenotypic presentation.
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ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia
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Summary
We report the successful delivery of a healthy baby after intracytoplasmic sperm injection (ICSI) with frozen-thawed autologous sperm, cryostored for 26 years, the longest successful autologous sperm cryostorage reported. Sperm was cryostored for a 15-year-old boy at the time of his cancer diagnosis. Semen samples were frozen with cryoprotectant, using a graduated vapour-phase nitrogen protocol. Straws were stored in a large vapour-phase nitrogen tank until transfer for use. The couple underwent a single ICSI–in vitro fertilisation procedure using the frozen-thawed sperm with a transfer of five fertilised embryos, resulting in the live birth of a healthy baby boy. This reinforces the importance of offering sperm cryopreservation to men who have not completed their family prior to gonadotoxic treatment for cancer or other diseases. As practical, low-cost fertility insurance, it should be offered to any young man who can collect semen and it provides essentially unlimited duration of fertility preservation.
Learning points
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Gonadotoxic chemo or radiotherapy treatment for cancer or other diseases usually causes temporary or permanent male infertility.
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Sperm cryostorage serves as a practical, low-cost insurance to facilitate future paternity.
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All men who have not completed their families and are scheduled for gonadotoxic treatments should be offered sperm cryostorage.
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There is no lower age limit for young men who can collect semen.
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Sperm cryostorage offers essentially indefinite duration for the preservation of male fertility.
Search for other papers by Benthe A M Dijkman in
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Summary
A 31-year-old woman with complete androgen insensitivity syndrome (CAIS) experienced breast volume fluctuations during biphasic hormone replacement therapy consisting of estradiol and cyclical dydrogesterone, a progestin. 3D breast volume measurements showed a 100 cc volume (17%) difference between estradiol monotherapy and combined estradiol and dydrogesterone treatment. Progestogen-dependent breast volume changes have not been reported in the literature. Our findings suggest a correlation between progestogen use and breast volume. Due to the rapid cyclical changes, we hypothesize that the effect is caused by fluid retention.
Learning points
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There is limited reports available on the effects of progesterone on breast development and volume.
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3D imaging provides an easy-to-use method to quantify breast volume.
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The patient in our case description clearly showed that cyclic progesterone use might induce substantial cyclic changes in breast volume.
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In women with complete androgen insensitivity syndrome (CAIS), monotherapy with estrogen or continuous supplementation of progesterone might be preferable over cyclic progesterone use.
Department of Pediatrics, The University of Tokyo Hospital, Tokyo, Japan
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Summary
Prader–Willi syndrome (PWS) is a genetic imprinting disorder that is characterized by obesity, short stature, and hypogonadism. Hypogonadism is characterized by normal luteinizing hormone (LH), high follicle-stimulating hormone (FSH), low testosterone, low inhibin B, and relatively low anti-Müllerian hormone (AMH). Only a few cases of central precocious puberty (CPP) have been reported in PWS, and follow-up for CPP with PWS is not established. Hence, we present a boy with PWS accompanied by CPP. Gonadotropin-releasing hormone analog (GnRHa) therapy was started at 7 years of age, CPP was adequately arrested, and GnRHa therapy was discontinued at 11.3 years of age. Growth hormone (GH) therapy was started at 12 years of age due to inadequate growth. He grew close to his final height, and his testes developed with normal LH, increased FSH, normal testosterone, and reduced AMH corresponding to puberty at 13.5 years of age. The features of 16 patients with PWS with CPP, including our patient, were summarized. Out of seven male patients, five were treated with GnRHa, as well as four out of nine female patients. Out of 16 patients, 6 were assessed with pubertal development over 13 years of age. Pubertal development was considered to be restored in four patients who had GnRHa therapy discontinuation. We should carefully follow-up on pubertal development in CPP. GnRHa therapy is useful for adequate puberty blockage, and pubertal development could be restored with GnRHa therapy discontinuation.
Learning points
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Pubertal development in Prader–Willi syndrome (PWS) varies from hypogonadism to precocious puberty.
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Pubertal development assessment based on clinical features and hormone levels is needed in central precocious puberty (CPP) treatment with PWS.
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Gonadotropin-releasing hormone analog (GnRHa) therapy is useful for CPP with PWS, and pubertal development can be restored with GnRHa therapy discontinuation.
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Summary
Growth anomaly is a prominent feature in Wolf-Hirschhorn syndrome (WHS), a rare congenital disorder caused by variable deletion of chromosome 4p. While growth charts have been developed for WHS patients 0–4 years of age and growth data available for Japanese WHS patients 0–17 years, information on pubertal growth and final height among WHS children remain lacking. Growth hormone (GH) therapy has been reported in two GH-sufficient children with WHS, allowing for pre-puberty catch up growth; however, pubertal growth and final height information was also unavailable. We describe the complete growth journey of a GH-sufficient girl with WHS from birth until final height (FH), in relation to her mid parental height (MPH) and target range (TR). Her growth trajectory and pubertal changes during childhood, when she was treated with growth hormone (GH) from 3 years 8 months old till 6 months post-menarche at age 11 years was fully detailed.
Learning points:
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Pubertal growth characteristics and FH information in WHS is lacking.
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While pre-pubertal growth may be improved by GH, GH therapy may not translate to improvement in FH in WHS patients.
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Longitudinal growth, puberty and FH data of more WHS patients may improve the understanding of growth in its various phases (infancy/childhood/puberty).
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Summary
A case of follicular thyroid cancer with intense focal Methionine uptake on 11C-Methionine PET/CT is reported here. The use of 11C-Methionine PET in differentiated thyroid cancer is currently being investigated as a surrogate tracer compared to the more widely used 18F-FDG PET. This case illustrates the potential incremental value of this modality, not only in the localizing of parathyroid adenoma, but also indicating that 11C-Methionine PET might have a potential of increasing the pretest likelihood of thyroid malignancy in a cold nodule with highly increased Sestamibi uptake.
Learning points:
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11C-Methionine PET/CT and 18F-Fluorocholine PET/CT often visualizes the parathyroid adenoma in case of negative Tc-99m-MIBI SPECT/CT.
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A cold nodule in Tc-99m Pertechnetat thyroid scintigraphy with a negative Sestamibi scintigraphy has a very low probability of being malignant.
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However, the pretest likelihood of thyroid cancer in a cold nodule with increased Sestamibi uptake is low.
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11C-Methionine PET might have a potential incremental value in increasing the pretest likelihood of thyroid malignancy in a cold nodule with highly increased Sestamibi uptake.
