Diagnosis and Treatment > Investigation > Testosterone
You are looking at 31 - 40 of 72 items
Search for other papers by Irene Berges-Raso in
Google Scholar
PubMed
Search for other papers by Olga Giménez-Palop in
Google Scholar
PubMed
Search for other papers by Elisabeth Gabau in
Google Scholar
PubMed
Search for other papers by Ismael Capel in
Google Scholar
PubMed
Search for other papers by Assumpta Caixàs in
Google Scholar
PubMed
Search for other papers by Mercedes Rigla in
Google Scholar
PubMed
Summary
Kallmann syndrome is a genetically heterogeneous form of hypogonadotropic hypogonadism caused by gonadotropin-releasing hormone deficiency and characterized by anosmia or hyposmia due to hypoplasia of the olfactory bulbs; osteoporosis and metabolic syndrome can develop due to longstanding untreated hypogonadism. Kallmann syndrome affects 1 in 10 000 men and 1 in 50 000 women. Defects in 17 genes, including KAL1, have been implicated. Kallmann syndrome can be associated with X-linked ichthyosis, a skin disorder characterized by early onset dark, dry, irregular scales affecting the limb and trunk, caused by a defect of the steroid sulfatase gene (STS). Both KAL1 and STS are located in the Xp22.3 region; therefore, deletions in this region cause a contiguous gene syndrome. We report the case of a 32-year-old man with ichthyosis referred for evaluation of excessive height (2.07 m) and weight (BMI: 29.6 kg/m2), microgenitalia and absence of secondary sex characteristics. We diagnosed Kallmann syndrome with ichthyosis due to a deletion in Xp22.3, a rare phenomenon.
Learning points:
-
Kallmann syndrome is a genetically heterogeneous disease characterized by hypogonadotropic hypogonadism with anosmia or hyposmia associated with defects in the production or action of gonadotropin-releasing hormone (GnRH) and hypoplasia of the olfactory bulbs.
-
Several genes have been implicated in Kallmann syndrome, including KAL1, located in the Xp22.3 region, which is responsible for X-linked Kallmann syndrome. KAL1 encodes the protein anosmin-1. X-linked ichthyosis is caused by deficiency of the steroid sulfatase enzyme, encoded by STS, which is also located in the Xp22.3 region. Deletions involving this region can affect both genes and result in contiguous gene syndromes.
-
Phenotype can guide clinicians toward suspicion of a specific genetic mutation. KAL1 mutations are mostly related to microgenitalia, unilateral renal agenesis and synkinesia, although patients need not present all these abnormalities.
-
Longstanding untreated hypogonadism is associated with poor sexual health, osteoporosis and metabolic syndrome with the concomitant risk of developing type 2 diabetes mellitus and obesity.
-
Treatment aims to promote the development of secondary sex characteristics, build and sustain normal bone and muscle mass and restore fertility. Treatment can also help minimize some psychological consequences.
-
Treatments available for patients with congenital GnRH deficiency such as Kallmann syndrome include gonadal steroid hormones, human gonadotropins and GnRH. The choice of therapy depends on the goal or goals.
Search for other papers by Ana Coelho Gomes in
Google Scholar
PubMed
Search for other papers by José Maria Aragüés in
Google Scholar
PubMed
Search for other papers by Sílvia Guerra in
Google Scholar
PubMed
Search for other papers by Joana Fernandes in
Google Scholar
PubMed
Search for other papers by Mário Rui Mascarenhas in
Google Scholar
PubMed
Summary
Hypogonadotropic hypogonadism (HH) is common and occurs prematurely in HIV-infected men. However, HH with very low testosterone has not been described. Three men with normal pubertal development and HIV1 diagnosis at the ages of 22, 34 and 35 years. All complained of decreased libido, anejaculation and erectile dysfunction thirteen years, six months and one year after HIV diagnosis, respectively. Two had depressive syndrome and two were treated with antiretroviral therapy. Laboratory tests revealed isolated HH in all. Sellar and head CT scans were normal and all had normal CD4 count. They started testosterone replacement therapy, with symptoms improvement. Causes of HH in HIV-infected men include undernutrition, severe illness, drugs, pituitary dysfunction and comorbidities. Despite having none of these conditions (except two that were treated with low-dose psychotropics), our patients had HH with uncommonly low testosterone. This suggests that a different mechanism contributes to severe HH in HIV-infected men.
Learning points:
-
The pathogenesis of hypogonadotropic hypogonadism in HIV-infected men is multifactorial and androgen deficiency is more often a consequence of secondary hypogonadism than primary hypogonadism.
-
Causes of hypogonadotropic hypogonadism in HIV-infected men include undernutrition, severe illness, drugs (psychotropics, opiates, megestrol acetate or steroids), pituitary dysfunction (tumor, hyperprolactinemia), an AIDS-related lesion (very rarely) and comorbid conditions, such as antibody to hepatitis C virus seropositivity and injection drug use.
-
Highly active antiretroviral therapy (HAART), particularly protease inhibitor therapy has been associated with sexual dysfunction in men, but the causal nature of this relation has not been clearly established.
-
Hypogonadotropic hypogonadism with uncommonly low testosterone levels are not usually associated with the conditions referred and this suggests that a different mechanism could contribute to severe hypogonadotropic hypogonadism in HIV-infected men.
-
Screening for hypogonadism in all HIV-infected men might help to understand its etiology.
Search for other papers by Khaled Aljenaee in
Google Scholar
PubMed
Search for other papers by Sulaiman Ali in
Google Scholar
PubMed
Search for other papers by Seong Keat Cheah in
Google Scholar
PubMed
Search for other papers by Owen MacEneaney in
Google Scholar
PubMed
Search for other papers by Niall Mulligan in
Google Scholar
PubMed
Search for other papers by Neil Hickey in
Google Scholar
PubMed
Search for other papers by Tommy Kyaw Tun in
Google Scholar
PubMed
Search for other papers by Seamus Sreenan in
Google Scholar
PubMed
Search for other papers by John H McDermott in
Google Scholar
PubMed
Markedly elevated androgen levels can lead to clinical virilization in females. Clinical features of virilization in a female patient, in association with biochemical hyperandrogenism, should prompt a search for an androgen-producing tumor, especially of ovarian or adrenal origin. We herein report the case of a 60-year-old woman of Pakistani origin who presented with the incidental finding of male pattern baldness and hirsutism. Her serum testosterone level was markedly elevated at 21 nmol/L (normal range: 0.4–1.7 nmol/L), while her DHEAS level was normal, indicating a likely ovarian source of her elevated testosterone. Subsequently, a CT abdomen-pelvis was performed, which revealed a bulky right ovary, confirmed on MRI of the pelvis as an enlarged right ovary, measuring 2.9 × 2.2 cm transaxially. A laparoscopic bilateral salpingo-oophorectomy was performed, and histopathological examination and immunohistochemistry confirmed the diagnosis of a Leydig cell tumor, a rare tumor accounting for 0.1% of ovarian tumors. Surgical resection led to normalization of testosterone levels.
Learning points:
-
Hirsutism in postmenopausal women should trigger suspicion of androgen-secreting tumor
-
Extremely elevated testosterone level plus normal DHEAS level point toward ovarian source
-
Leydig cell tumor is extremely rare cause of hyperandrogenicity
Search for other papers by Judith Gerards in
Google Scholar
PubMed
Search for other papers by Michael M Ritter in
Google Scholar
PubMed
Search for other papers by Elke Kaminsky in
Google Scholar
PubMed
Search for other papers by Andreas Gal in
Google Scholar
PubMed
Search for other papers by Wolfgang Hoeppner in
Google Scholar
PubMed
Search for other papers by Marcus Quinkler in
Google Scholar
PubMed
Summary
DAX1 (NR0B1) is an orphan nuclear receptor, which plays an important role in development and function of the adrenal glands and gonads. Mutations in DAX1 cause X-linked adrenal hypoplasia congenita (X-linked AHC), which is characterized by adrenal insufficiency (AI) and hypogonadotropic hypogonadism (HHG). Affected boys present with adrenal failure usually in childhood and, later in life, with delayed puberty. However, patients with a late-onset form of X-linked AHC have also been described in the past years. We report a male patient who presented with symptoms of an adrenal crisis at the age of 38 years and was later diagnosed with HHG. Family history was positive with several male relatives diagnosed with AI and compatible with the assumed X-chromosomal inheritance of the trait. Direct sequencing of DAX1 of the patient revealed a hemizygous cytosine-to-thymine substitution at nucleotide 64 in exon 1, which creates a novel nonsense mutation (p.(Gln22*)). In order to compare the clinical presentation of the patient to that of other patients with X-linked AHC, we searched the electronic database MEDLINE (PubMed) and found reports of nine other cases with delayed onset of X-linked AHC. In certain cases, genotype–phenotype correlation could be assumed.
Learning points:
-
X-linked AHC is a rare disease characterized by primary AI and hypogonadotropic hypogonadism (HHG). The full-blown clinical picture is seen usually only in males with a typical onset in childhood.
-
Patients with a late-onset form of X-linked AHC have also been described recently. Being aware of this late-onset form might help to reach an early diagnosis and prevent life-threatening adrenal crises.
-
Adult men with primary AI of unknown etiology should be investigated for HHG. Detecting a DAX1 mutation may confirm the clinical diagnosis of late-onset X-linked AHC.
-
In relatives of patients with genetically confirmed X-linked AHC, targeted mutation analysis may help to identify family members at risk and asymptomatic carriers, and discuss conscious family planning.
Search for other papers by Ahmad Haider in
Google Scholar
PubMed
Search for other papers by Karim S Haider in
Google Scholar
PubMed
Research Department, Gulf Medical University, Ajman, UAE
Search for other papers by Farid Saad in
Google Scholar
PubMed
Summary
In daily practice, clinicians are often confronted with obese type 2 diabetes mellitus (T2DM) patients for whom the treatment plan fails and who show an inadequate glycemic control and/or no sustainable weight loss. Untreated hypogonadism can be the reason for such treatment failure. This case describes the profound impact testosterone therapy can have on a male hypogonadal patient with metabolic syndrome, resulting in a substantial and sustained loss of body weight, pronounced improvement of all critical laboratory values and finally complete remission of diabetes.
Learning points:
-
Hypogonadism occurs frequently in men with T2DM.
-
In case of pronounced abdominal fat deposition and T2DM, the male patient should be evaluated for testosterone deficiency.
-
Untreated hypogonadism can complicate the successful treatment of patients with T2DM.
-
Under testosterone therapy, critical laboratory values are facilitated to return back to normal ranges and even complete remission of diabetes can be achieved.
Search for other papers by Kingsley Okolie in
Google Scholar
PubMed
Australian National University Medical School, Canberra, ACT, Australia
Search for other papers by Sumathy Perampalam in
Google Scholar
PubMed
Search for other papers by Anthony Barker in
Google Scholar
PubMed
Australian National University Medical School, Canberra, ACT, Australia
Search for other papers by Christopher J Nolan in
Google Scholar
PubMed
Klinefelter syndrome (KS) is a chromosomal disorder affecting males, with the typical karyotype of 47,XXY due to a supernumerary X chromosome, which causes progressive testicular failure resulting in androgen deficiency and infertility. Despite it being the most common sex chromosomal disorder, its diagnosis is easily missed. In addition to its classical clinical features of tall stature, gynaecomastia, small testes, and symptoms and signs of hypogonadism including infertility, KS is also often associated with neurocognitive, behavioural and psychiatric disorders.
We present a 44-year-old man with KS who, despite having erectile dysfunction, paradoxically had increased libido. He used sildenafil to overcome his erectile dysfunction. Hypersexuality was manifested by very frequent masturbation, multiple sexual partners most of whom were casual, and a sexual offence conviction at the age of 17 years.
Discussion focuses on the frequent failure of clinicians to diagnose KS, the neurocognitive, behavioural and psychiatric aspects of KS, this unusual presentation of hypersexuality in a man with KS, and the challenges of medical management of hypogonadism in a man with a history of a sexual offence.
Learning points:
-
Klinefelter syndrome (KS) is common in men (about 1 in 600 males), but the diagnosis is very often missed.
-
In addition to classic features of hypogonadism, patients with KS can often have associated neurocognitive, behavioural and/or psychiatric disorders.
-
More awareness of the association between KS and difficulties related to verbal skills in boys could improve rates of early diagnosis and prevent longer-term psychosocial disability.
-
Hypersexuality in the context of hypogonadism raises the possibility of sex steroid independent mechanistic pathways for libido.
-
Testosterone replacement therapy in KS with hypersexuality should be undertaken with caution using a multidisciplinary team approach.
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Search for other papers by B Cangiano in
Google Scholar
PubMed
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Search for other papers by C Cacciatore in
Google Scholar
PubMed
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Search for other papers by L Persani in
Google Scholar
PubMed
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Search for other papers by M Bonomi in
Google Scholar
PubMed
We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH) determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate. The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values. Therefore, it was decided to switch to a restoration therapy with clomiphene citrate 25 mg/die, which resulted in the resolution of symptoms without evident side effects. In a couple of months, the patient showed normalization of testosterone levels and increment of testicular volume. Since secondary hypogonadism is the consequence of an insufficient stimulation of the gonads by hypothalamic–pituitary axis, therapeutic approaches aimed to restore endogenous testosterone production should be considered in alternative to testosterone replacement, particularly if side effects intervene. Among these strategies, clomiphene citrate seems to have a high efficacy and safety profile also in the elderly with isolated HH and no evident pituitary lesion.
Learning points:
-
Hypogonadism should always be assessed in patients with severe loss in BMD and undergo appropriate medical treatment.
-
In hypogonadotropic hypogonadism, more approaches are available other than testosterone replacement therapy alone.
-
In patients with severe late-onset central hypogonadism presenting with erythrocytosis even at low doses of replacement therapy, restoration therapy with clomiphene could prove to be an effective solution, particularly in patients with a reversible disruption of GNRH/gonadotropin functions.
-
Clomiphene citrate increases gonadotropin levels and testicular volume and should therefore be considered in hypogonadal men who wish to remain fertile.
ANZAC Research Institute, University of Sydney, Sydney, New South Wales, Australia
Search for other papers by Nandini Shankara Narayana in
Google Scholar
PubMed
Search for other papers by Anne-Maree Kean in
Google Scholar
PubMed
Central Clinical School, Sydney Medical School, University of Sydney, New South Wales, Australia
Search for other papers by Lisa Ewans in
Google Scholar
PubMed
Search for other papers by Thomas Ohnesorg in
Google Scholar
PubMed
Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
Search for other papers by Katie L Ayers in
Google Scholar
PubMed
Search for other papers by Geoff Watson in
Google Scholar
PubMed
Search for other papers by Arthur Vasilaras in
Google Scholar
PubMed
Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
Search for other papers by Andrew H Sinclair in
Google Scholar
PubMed
Search for other papers by Stephen M Twigg in
Google Scholar
PubMed
Search for other papers by David J Handelsman in
Google Scholar
PubMed
Summary
46,XX disorders of sexual development (DSDs) occur rarely and result from disruptions of the genetic pathways underlying gonadal development and differentiation. We present a case of a young phenotypic male with 46,XX SRY-negative ovotesticular DSD resulting from a duplication upstream of SOX9 presenting with a painful testicular mass resulting from ovulation into an ovotestis. We present a literature review of ovulation in phenotypic men and discuss the role of SRY and SOX9 in testicular development, including the role of SOX9 upstream enhancer region duplication in female-to-male sex reversal.
Learning points:
-
In mammals, the early gonad is bipotent and can differentiate into either a testis or an ovary. SRY is the master switch in testis determination, responsible for differentiation of the bipotent gonad into testis.
-
SRY activates SOX9 gene, SOX9 as a transcription factor is the second major gene involved in male sex determination. SOX9 drives the proliferation of Sertoli cells and activates AMH/MIS repressing the ovary. SOX9 is sufficient to induce testis formation and can substitute for SRY function.
-
Assessing karyotype and then determination of the presence or absence of Mullerian structures are necessary serial investigations in any case of DSD, except for mixed gonadal dysgenesis identified by karyotype alone.
-
Treatment is ideal in a multidisciplinary setting with considerations to genetic (implications to family and reproductive recurrence risk), psychological aspects (sensitive individualized counseling including patient gender identity and preference), endocrinological (hormone replacement), surgical (cosmetic, prophylactic gonadectomy) fertility preservation and reproductive opportunities and metabolic health (cardiovascular and bones).
Search for other papers by Athanasios Fountas in
Google Scholar
PubMed
Search for other papers by Zoe Giotaki in
Google Scholar
PubMed
Search for other papers by Evangelia Dounousi in
Google Scholar
PubMed
Search for other papers by George Liapis in
Google Scholar
PubMed
Search for other papers by Alexandra Bargiota in
Google Scholar
PubMed
Search for other papers by Agathocles Tsatsoulis in
Google Scholar
PubMed
Search for other papers by Stelios Tigas in
Google Scholar
PubMed
Summary
Proteinuric renal disease is prevalent in congenital or acquired forms of generalized lipodystrophy. In contrast, an association between familial partial lipodystrophy (FPLD) and renal disease has been documented in very few cases. A 22-year-old female patient presented with impaired glucose tolerance, hyperinsulinemia, hirsutism and oligomenorrhea. On examination, there was partial loss of subcutaneous adipose tissue in the face, upper and lower limbs, bird-like facies with micrognathia and low set ears and mild acanthosis nigricans. Laboratory investigations revealed hyperandrogenism, hyperlipidemia, elevated serum creatine kinase and mild proteinuria. A clinical diagnosis of FPLD of the non-Dunnigan variety was made; genetic testing revealed a heterozygous c.1045C > T mutation in exon 6 of the LMNA gene, predicted to result in an abnormal LMNA protein (p.R349W). Electromyography and muscle biopsy were suggestive of non-specific myopathy. Treatment with metformin and later with pioglitazone was initiated. Due to worsening proteinuria, a renal biopsy was performed; histological findings were consistent with mild focal glomerular mesangioproliferative changes, and the patient was started on angiotensin-converting enzyme inhibitor therapy. This is the fourth report of FPLD associated with the c.1045C > T missense LMNA mutation and the second with co-existent proteinuric renal disease. Patients carrying this specific mutation may exhibit a phenotype that includes partial lipodystrophy, proteinuric nephropathy, cardiomyopathy and atypical myopathy.
Learning points:
-
Lipodystrophy is a rare disorder characterized by the complete or partial loss of subcutaneous adipose tissue, insulin resistance, diabetes mellitus and hyperlipidemia.
-
Proteinuric renal disease is a prevalent feature of generalized lipodystrophy but rare in familial partial lipodystrophy.
-
Patients carrying the c.1045C > T missense LMNA mutation (p.R349W) may present with familial partial lipodystrophy, proteinuric nephropathy, cardiomyopathy and atypical myopathy.
Search for other papers by Gulay Simsek Bagir in
Google Scholar
PubMed
Search for other papers by Soner Civi in
Google Scholar
PubMed
Search for other papers by Ozgur Kardes in
Google Scholar
PubMed
Search for other papers by Fazilet Kayaselcuk in
Google Scholar
PubMed
Search for other papers by Melek Eda Ertorer in
Google Scholar
PubMed
Summary
Pituitary apoplexy (PA) may very rarely present with hiccups. A 32-year-old man with classical acromegaloid features was admitted with headache, nausea, vomiting and stubborn hiccups. Pituitary magnetic resonance imaging (MRI) demonstrated apoplexy of a macroadenoma with suprasellar extension abutting the optic chiasm. Plasma growth hormone (GH) levels exhibited suppression (below <1 ng/mL) at all time points during GH suppression test with 75 g oral glucose. After treatment with corticosteroid agents, he underwent transsphenoidal pituitary surgery and hiccups disappeared postoperatively. The GH secretion potential of the tumor was clearly demonstrated immunohistochemically. We conclude that stubborn hiccups in a patient with a pituitary macroadenoma may be a sign of massive apoplexy that may result in hormonal remission.
Learning points:
-
Patients with pituitary apoplexy may rarely present with hiccups.
-
Stubborn hiccupping may be a sign of generalized infarction of a large tumor irritating the midbrain.
-
Infarction can be so massive that it may cause cessation of hormonal overproduction and result in remission.