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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.
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
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Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
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Department of General Surgery, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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Summary
Spontaneous remission of primary hyperparathyroidism (PHPT) due to necrosis and haemorrhage of parathyroid adenoma, the so-called ‘parathyroid auto-infarction’ is a very rare, but previously described phenomenon. Patients usually undergo parathyroidectomy or remain under close clinical and biochemical surveillance. We report two cases of parathyroid auto-infarction diagnosed in the same tertiary centre; one managed surgically and the other conservatively up to the present time. Case #1 was a 51-year old man with PHPT (adjusted (adj.) calcium: 3.11 mmol/L (reference range (RR): 2.20–2.60 mmol/L), parathyroid hormone (PTH) 26.9 pmol/L (RR: 1.6–6.9 pmol/L) and urine calcium excretion consistent with PHPT) referred for parathyroidectomy. Repeat biochemistry 4 weeks later at the surgical clinic showed normal adj. calcium (2.43 mmol/L) and reduced PTH. Serial ultrasound imaging demonstrated reduction in size of the parathyroid lesion from 33 to 17 mm. Twenty months later, following recurrence of hypercalcaemia, he underwent neck exploration and resection of an enlarged right inferior parathyroid gland. Histology revealed increased fibrosis and haemosiderin deposits in the parathyroid lesion in keeping with auto-infarction. Case #2 was a 54-year-old lady admitted with severe hypercalcaemia (adj. calcium: 4.58 mmol/L, PTH 51.6 pmol/L (RR: 1.6–6.9 pmol/L)) and severe vitamin D deficiency. She was treated with intravenous fluids and pamidronate and 8 days later developed symptomatic hypocalcaemia (1.88 mmol/L) with dramatic decrease of PTH (17.6 pmol/L). MRI of the neck showed a 44 mm large cystic parathyroid lesion. To date, (18 months later), she has remained normocalcaemic.
Learning points:
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Primary hyperparathyroidism (PHPT) is characterised by excess parathyroid hormone (PTH) secretion arising mostly from one or more autonomously functioning parathyroid adenomas (up to 85%), diffuse parathyroid hyperplasia (<15%) and in 1–2% of cases from parathyroid carcinoma.
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PHPT and hypercalcaemia of malignancy, account for the majority of clinical presentations of hypercalcaemia.
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Spontaneous remission of PHPT due to necrosis, haemorrhage and infarction of parathyroid adenoma, the so-called ‘parathyroid auto-infarction’, ‘auto-parathyroidectomy’ or ‘parathyroid apoplexy’ is a very rare in clinical practice but has been previously reported in the literature.
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In most cases, patients with parathyroid auto-infarction undergo parathyroidectomy. Those who are managed conservatively need to remain under close clinical and biochemical surveillance long-term as in most cases PHPT recurs, sometimes several years after auto-infarction.
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Summary
Gonadotrophin therapy with human chorionic gonadotrophin and recombinant FSH is indicated for use in men with reduced spermatogenesis due to hypogonadotrophic hypogonadism (HH). Patients require regular monitoring for side effects and desired response to treatment. We present a man with HH, azoospermia and a history of previous anabolic steroid usage who had undergone gonadotrophin therapy, had subsequently achieved conception and has now fathered a child.
Learning points
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In total, 15% of couples do not achieve pregnancy within 1 year and seek medical treatment for infertility: male factors contribute to 50% of these.
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The evaluation of male infertility should include a full history and examination, an endocrine profile and a quality-controlled semen analysis.
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HH with defective spermatogenesis is an important cause of male infertility in a small percentage of cases.
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Gonadotrophin therapy requires regular monitoring for side effects and desired response to treatment.
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Any sustained rise in prostate specific antigen levels should prompt urological assessment for possible prostate biopsy.
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A multidisciplinary approach is required for gonadotrophin therapy, especially if assisted fertilisation techniques are required once, spermatogenesis is achieved.
