Ruth CaseyDepartments of Diabetes and Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK Department of Medical Genetics, University of Cambridge and NIHR Cambridge Biomedical Research Centre and Cancer Research UK Cambridge Centre, Cambridge, UK
Activating mutations in AVPR2 are associated with nephrogenic syndrome of inappropriate antidiuresis (NSIAD). NSIAD causes hyponatremia, decreased serum osmolality and clinical symptoms, which may present from birth or in infancy and include hypotonia, irritability, vomiting and/or seizures. Symptoms in later life are often less specific and include malaise, dizziness, confusion, tiredness and headache. NSIAD is a rare X-linked condition, which is associated with a variable phenotype in males, of whom some present in infancy but others do not become symptomatic until adulthood, or occasionally, never. Female carriers may present with episodes of hyponatremia, usually found incidentally. Literature in this field is limited; namely, two clinical reports describing a female proband, both diagnosed in infancy. We describe, for the first time, the case of an adult female proband with NSIAD, who had longstanding associated symptoms of tiredness, headache, temporary memory loss and mood changes as well as hyponatremia and decreased serum osmolality. A water load test demonstrated an inability to dilute urine and gene sequencing confirmed a recurrent activating mutation in AVPR2. The variant was inherited from the proband’s mother who had had longstanding episodes of transient asymptomatic hyponatremia. This is the third report of a female proband with NSIAD and is the first female reported who sought medical treatment for chronic symptoms from adulthood. This case acts as a reminder of the importance of considering NSIAD as a diagnosis in females of all ages with unexplained hyponatremia.
Activating mutations in the AVPR2 gene are associated with the rare X-linked condition nephrogenic syndrome of inappropriate antidiuresis.
NSIAD is associated with hyponatremia, decreased serum osmolality and inappropriately increased urinary osmolality. Early clinical symptoms in infancy include hypotonia, irritability, vomiting and/or seizures. Symptoms in later life include malaise, dizziness, confusion, tiredness and headache.
NSIAD should be considered in female, as well as male, patients who present with unexplained hyponatremia and decreased serum osmolality. Family history may reveal relevant symptoms or biochemical features in other family members. However, family history may not always be informative due to the variable nature of the condition or if the proband has a de novo pathogenic variant.
A water load test with measurement of AVP may be informative in distinguishing NSIAD from SIADH. Measurement of co-peptin levels may be considered, in substitution for direct measurement of AVP.
Patients with NSIAD should be counseled about appropriate daily fluid volume intake. Potential episodes of fluid overload should be avoided.
Poli Mara SpritzerGynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clinicas de Porto Alegre, Brazil Laboratory of Molecular Endocrinology, Department of Physiology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
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.
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.
A previously healthy 32-year-old woman developed cyclical mood swings after being prescribed cabergoline for a pituitary microprolactinoma. These mood swings persisted for over 2 years, at which point she developed an acute manic episode with psychotic features and was admitted to a psychiatry unit. Cabergoline was discontinued and replaced with aripiprazole 10 mg/day. Her manic episode quickly resolved, and she was discharged within 6 days of admission. The aripiprazole suppressed her prolactin levels for over 18 months of follow-up, even after the dose was lowered to 2 mg/day. There was no significant change in tumor size over 15 months, treatment was well tolerated. However, after 9 months of taking 2 mg aripiprazole, she developed brief manic symptoms, and the dose was returned to 10 mg daily, with good effect.
Dopamine agonists such as cabergoline, which are a standard treatment for microprolactinomas, can have serious adverse effects such as psychosis or valvular heart disease.
Aripiprazole is a well-tolerated atypical antipsychotic that, unlike other antipsychotics, is a partial dopamine agonist capable of suppressing prolactin levels.
Adjunctive, low-dose aripiprazole has been utilized to reverse risperidone-induced hyperprolactinemia.
This case report demonstrates how aripiprazole monotherapy, in doses ranging from 2 to 10 mg/day, was effective in suppressing prolactin in a woman with a microprolactinoma who developed psychiatric side effects from cabergoline.