[Polyendocrine syndromes in dogs]. / Polyendokrine Syndrome beim Hund.

The autoimmune polyendocrine syndrome (APS) refers to a combination of autoimmune endocrine disorders. It is rarely described in dogs. The most common combinations are hypoadrenocorticism and hypothyroidism, followed by diabetes mellitus, and less often hypoparathyroidism and orchitis. The diagnosis of the APS is based on the diagnosis of each endocrinopathy, as is the therapy, which involves the substitution of deficient hormones. If a patient was previously stable under treatment and is showing further signs (e.g. polyuria, polydipsia, or weight loss), the development of additional endocrinopathies like hypoadrenocorticism or diabetes mellitus should be considered. The diagnosis of the initially diagnosed endocrinopathy should also be critically questioned. This article summarizes some cases of our own animal hospital and selected cases published in the available literature.

Prevalence of the RAPGEF5 c.2624C>A and PLOD1 c.2032G>A variants associated with equine familial isolated hypoparathyroidism and fragile foal syndrome in the US Thoroughbred population (1988-2019).

BACKGROUND: Equine familial isolated hypoparathyroidism (EFIH) and fragile foal syndrome (FFS) are both fatal recessive conditions reported in Thoroughbred foals. The causal variants for EFIH (RAPGEF5 c.2624C>A; EquCab3.0. chr4: g.54108297G>T) and FFS (PLOD1 c.2032G>A; EquCab3.0, chr2: g.39927817) were recently reported. Prevalence assessment for these variants in a large cohort of samples is needed to provide evidence-based recommendations for genetic testing. OBJECTIVES: To estimate the frequency of the EFIH and FFS variant alleles in the United States Thoroughbred population between 1988 and 2019, and determine whether these are recent mutations or are increasing in frequency due to current breeding practices. STUDY DESIGN: Population allele frequency study. METHODS: Genomic DNA from hair and serum samples were genotyped for the EFIH and FFS. Allele frequencies between cohorts, based on year of birth (1988-2000, n = 728) and (2001-2019, n = 1059), as well as across the seven geographical regions of the United States were compared by Fisher's Exact tests. RESULTS: EFIH and FFS allele frequencies were not significantly different between the two time points studied (0.008 and 0.004, respectively, in the older cohorts and 0.008 and 0.009 in most recent years). No EFIH or FFS homozygotes were detected. A sample from 1992 was identified as a carrier for EFIH and one from 1993 a carrier for FFS. Non-significant changes in geographical distribution of carriers for both traits were observed. MAIN LIMITATIONS: The earliest samples available for study were from foals born in 1988. CONCLUSIONS: The EFIH and FFS variants are present at low frequency in the United States Thoroughbred population but are not recent mutations. There is no evidence to support changes in allele frequency over time. However, given the closed studbook and breeding practices, continued monitoring of breed allele frequencies and genetic testing is recommended to avoid the mating of carriers and production of affected foals.

Primary Hypoparathyroidism and Recurring Hypocalcemia in a Quarter Horse Gelding-A Case Report.

Hypoparathyroidism is an uncommon endocrine disorder in the horse characterized by a transient or permanent parathyroid hormone insufficiency. Hypoparathyroidism is associated with hypocalcemia and hyperphosphatemia, primarily presenting with clinical signs consistent with hypocalcemia. This case report describes clinical presentation and treatment of a horse with severe hypocalcemia due to primary hypoparathyroidism. A 17-year-old, 542 kg Quarter Horse gelding presented for shaking and tremors. Significant findings include generalized muscle fasciculations, synchronous diaphragmatic flutter, and a markedly hypermetric hindlimb gait. Hematology revealed a moderate hyperkalemia, hyperphosphatemia, hypomagnesemia, and severe hypocalcemia. Initial treatment consisted of oral and intravenous calcium supplementation and fluid therapy. Thirty-six hours after presentation, clinical signs resolved, and treatment was discontinued. Clinical signs reoccurred after the discontinuation of treatment. A presumptive diagnosis of primary hypoparathyroidism was made based on low parathyroid hormone in the presence of low ionized calcium. The patient was maintained on oral calcium carbonate (feed grade lime) and vitamin AED supplementation. Hypoparathyroidism is rare but oral supplementation of calcium with calcium carbonate resulted in a favorable outcome with no apparent decrease in performance. Long-term supplementation may be required to prevent disease recurrence.

Pelvic fracture triggering symptoms of an underlying primary hypoparathyroidism in an adult spayed bitch: A case report.

A 7-year-old mixed breed spayed bitch (body weight: 10.6 kg) was presented with a history of intermittent episodes of seizures and untreated limb fracture. Appetite loss, nervousness, lateral recumbency, fasciculations, ataxia and poor nutritional condition were found. Venous blood gas analysis highlighted normal acid-base balance and severe low ionized calcium (0.58 mEq/L [range 1.13-1.32 mEq/L]). Marked total hypocalcaemia (6.4 mg/dL [range 8-10] or 1.6 mM [range: 2-2.5]) associated with hyperphosphoraemia (9.3 mg/dl [range 3.5-6.5 mg/dl]) displayed inverted ratio between minerals. ECG showed sinus arrhythmias. Circulating levels of Mg and Cu were within physiological range (1.97 mg/dl and 128 µg/dl respectively) and effects from interactions were excluded. Oral administration of calcitriol at 40 ng/kg/day led to clinical improvement within 48 hours, but circulating iCa levels were still below the lower limit of the reference range. Baseline levels of circulating parathormone (PTH) were 3 pg/ml, along with normal values of circulating vitamin D. Primary hypoparathyroidism was diagnosed as a chronic underlying condition triggered by pelvic fracture.

A nonsense variant in Rap Guanine Nucleotide Exchange Factor 5 (RAPGEF5) is associated with equine familial isolated hypoparathyroidism in Thoroughbred foals.

Idiopathic hypocalcemia in Thoroughbred (TB) foals causes tetany and seizures and is invariably fatal. Based upon the similarity of this disease with human familial hypoparathyroidism and occurrence only in the TB breed, we conducted a genetic investigation on two affected TB foals. Familial hypoparathyroidism was identified, and pedigree analysis suggested an autosomal recessive (AR) mode of inheritance. We performed whole-genome sequencing of the two foals, their unaffected dams and four unaffected, unrelated TB horses. Both homozygosity mapping and an association analysis were used to prioritize potential genetic variants. Of the 2,808 variants that significantly associated with the phenotype using an AR mode of inheritance (P<0.02) and located within a region of homozygosity, 1,507 (54%) were located in a 9.7 Mb region on chr4 (44.9-54.6 Mb). Within this region, a nonsense variant (RAPGEF5 c.2624C>A,p.Ser875*) was significantly associated with the hypoparathyroid phenotype (Pallelic = 0.008). Affected foals were homozygous for the variant, with two additional affected foals subsequently confirmed in 2019. Necropsies of all affected foals failed to identify any histologically normal parathyroid glands. Because the nonsense mutation in RAPGEF5 was near the C-terminal end of the protein, the impact on protein function was unclear. Therefore, we tested the variant in our Xenopus overexpression model and demonstrated RAPGEF5 loss-of-function. This RAPGEF5 variant represents the first genetic variant for hypoparathyroidism identified in any domestic animal species.

Trauma-induced primary hypoparathyroidism following severe bite wound injury to the neck in a dog.

OBJECTIVE: To describe the clinical presentation and outcome of a dog with primary hypoparathyroidism secondary to cervical bite wounds. CASE SUMMARY: A 3-year-old male intact Chihuahua presented after being attacked by a large breed dog. The dog sustained severe cervical lacerations, exposing the trachea and jugular veins. A portion of the right thyroid gland was missing. The dog was stabilized before wound debridement and closure. Ionized calcium concentrations were within reference range at the time of presentation. Forty-eight hours after the initial trauma, the dog was presented in lateral recumbency with signs of hypovolemic shock, muscle tremors, and hyperthermia. Bloodwork showed severe ionized hypocalcemia with low normal parathyroid hormone concentration consistent with acute primary hypoparathyroidism. The dog was managed initially with IV calcium gluconate and calcitriol, then long-term oral calcium carbonate and vitamin D3. After 6 months, the dog was successfully weaned off calcium supplementation. NEW OR UNIQUE INFORMATION PROVIDED: This is the first described case of traumatic primary hypoparathyroidism after a bite injury to the neck in a dog.

Hipoparatireoidismo secundário ao uso prolongado de omeprazol em um cão: relato de caso / Secondary hypoparathyroidism to omeprazole prolonged use in a dog: case report

O hipoparatireoidismo, quer seja primário ou secundário, é uma doença rara em cães, causada pela diminuição da secreção de paratormônio pelas paratireoides, que leva a sinais clínicos resultantes da hipocalcemia. O omeprazol vem sendo cada vez mais utilizado na medicina veterinária visando à diminuição na produção de líquor, mas existem poucos estudos sobre os efeitos colaterais relacionados ao uso crônico dessa medicação. Relata-se o caso de um cão macho da raça Yorkshire Terrier, com quatro anos de idade, com sinais clínicos de dor, sendo verificada calcificação em pelve e divertículo renal. Segundo o proprietário, o cão fazia uso de omeprazol há mais de dois anos devido ao histórico de hidrocefalia. Os exames laboratoriais evidenciaram anemia microcítica hipocrômica, hipocalemia, hiperfosfatemia, hipocalcemia, hipomagnesemia e hipercalciúria. A dosagem do paratormônio sérico confirmou o hipoparatireoidismo. Após a suspensão do omeprazol, as alterações encontradas nos exames se normalizaram, confirmando que a causa do hipoparatireoidismo era o uso crônico da medicação.(AU)

Primary or secondary hypoparathyroidism is a rare disease in dogs caused by the decreased secretion of parathormone from the parathyroid glands, leading to clinical signs of hypocalcemia. Omeprazole has been increasingly used in veterinary medicine in order to reduce the production of cerebrospinal fluid, but there are few reports of side effects related to its chronic use. We report a case of a four-year-old male Yorkshire terrier with clinical signs of pain, calcification in the pelvis and renal diverticulum. According to the owner, the dog had been receiving omeprazole for over 2 years because of the history of hydrocephalus. Hematological exams revealed hypochromic microcytic anemia, hypokalemia, hyperphosphatemia, hypocalcemia, hypomagnesemia besides hypercalciuria. The determination of serum parathyroid hormone concentrations confirmed hypoparathyroidism. After interrupting omeprazole, the altered features on the exams returned to normal values, confirming that the cause of hypoparathyroidism was the chronic use of the drug.(AU)

Presumptive Glucocorticoid-Induced Refractory Hypocalcemia in a Dog with Idiopathic Immune-Mediated Hypoparathyroidism, Thrombocytopenia, and Hemolytic Anemia.

Clinically relevant hypocalcemia is a well-documented complication of glucocorticoid administration in people with hypoparathyroidism. The current report describes the phenomenon in a dog. A 7 yr old neutered male Pomeranian was diagnosed with immune-mediated thrombocytopenia, immune-mediated hemolytic anemia, and primary hypoparathyroidism. This dog required long-term parenteral calcium gluconate to prevent clinical hypocalcemia despite appropriate doses of oral calcitriol and calcium carbonate. This is the first description of clinically significant presumptive glucocorticoid induced hypocalcemia in a dog with primary hypoparathyroidism.

Synchronous Diaphragmatic Flutter Secondary to Primary Hypoparathyroidism in a Dog.

A 3 yr old, spayed, female miniature mchnauzer was presented for rhythmic, spontaneous contractions of the abdominal wall and across the costal arches. The rate of contractions coincided with the heart rate and increased during exercise. The dog was diagnosed with primary hypoparathyroidism based on low plasma ionized calcium and serum parathyroid hormone (PTH) concentrations. Fluoroscopic exam confirmed the diagnosis of a synchronous diaphragmatic flutter. Treatment of the hypocalcemia led to resolution of the diaphragmatic flutter.

Canine hypoparathyroidism: case report / Hipoparatireoidismo canino: relato de caso

Primary hypoparathyroidism is an uncommon endocrinopathy in dogs, resulting from absolute or relative deficiency in the secretion of parathormone (PTH). The dog presented signs of hypocalcemia, including muscular spasms, tetany and cramps, evolving to tonic-clonic seizures and fever. Emergency therapy for hypocalcemia included glucose physiological solution at 0.45% and calcium gluconate administered intravenously. Diagnosis was confirmed by the presence of hypocalcemia, hyperphosphatemia and a decrease in parathormone (PTH).(AU)

O hipoparatireoidismo primário é uma endocrinopatia incomum em cães, resultante da deficiência absoluta ou relativa na secreção do paratormônio (PTH). O cão apresentava sinais de hipocalcemia, incluindo espasmos musculares, tetania e cãibras que evoluíram para convulsões tônico-clônicas e febre. A terapia de emergência para hipocalcemia incluiu solução glicofisiológica 0,45% e gluconato de cálcio por intravenosa. O diagnóstico foi confirmado pela presença de hipocalcemia, hiperfosfatemia e diminuição do paratormônio (PTH).(AU)

Suspected primary hypoparathyroidism in a domestic ferret (Mustela putorius furo).

CASE DESCRIPTION: A 4-year-old castrated male domestic ferret (Mustela putorius furo) was examined because of a 3-week history of intermittent seizures, signs of depression, hypocalcemia, and hyperphosphatemia. CLINICAL FINDINGS: Plasma biochemical analysis confirmed hyperphosphatemia (17.7 mg/dL) and low concentrations of total (4.3 mg/dL) and ionized (0.49 mmol/L) calcium. Serum parathyroid hormone concentration (2.30 pmol/L) was low or in the low part of the reference interval. TREATMENT AND OUTCOME: Calcium gluconate was administered (2.0 mg/kg/h [0.9 mg/lb/h], IV), followed by a transition to administration of calcium carbonate (53 mg/kg [24.1 mg/lb], PO, q 12 h) and dihydrotachysterol (0.02 mg/kg/d [0.009 mg/lb/d], PO). Attitude of the ferret improved and seizures ceased as blood calcium concentrations increased. The ferret was reexamined because of seizures approximately 1 year after oral maintenance administration of dihydrotachysterol and calcium was initiated. The ferret responded well to emergency and long-term treatment but then was lost to follow-up monitoring. The ferret died approximately 2 years after the initial evaluation and treatment. Hypertrophic cardiomyopathy was diagnosed during necropsy, but the parathyroid glands could not be identified. CLINICAL RELEVANCE: To the authors' knowledge, primary hypoparathyroidism has not previously been reported in a ferret. The condition should be considered for ferrets with hypocalcemia and hyperphosphatemia without azotemia. Treatment with dihydrotachysterol and oral supplementation of calcium appeared to be a viable option for long-term management.

Progressive alopecia associated with hypoparathyroidism in a Jersey heifer.

BACKGROUND: Chronic progressive generalized alopecia in dairy cattle has been anecdotally discussed in veterinary forums. OBJECTIVE: To describe subclinical changes in an otherwise apparently healthy animal with chronic progressive generalized alopecia. ANIMALS: One 10-month-old Jersey heifer. METHODS: Case report. RESULTS: A heifer was presented for chronic progressive alopecia. The skin was hyperpigmented and very thin (2.4 ± 0.0 mm, compared with 8.1 ± 0.3 mm measured in four contemporaneous Jersey heifers). Histopathological examination of the skin revealed severe epidermal hyperplasia, orthokeratotic hyperkeratosis and diffuse follicular atrophy. Clinicopathological changes included hypocalcaemia that did not respond to calcium therapy. Serum parathyroid hormone (PTH) was not detected, compared with 1.38 ± 0.78 pmol/L in four contemporaneous Jersey heifers. A diagnosis of hypoparathyroidism was made based on hypocalcaemia and low PTH in the presence of normal magnesium levels. The heifer was otherwise healthy and was allowed to continue normal life. A spontaneous abortion occurred at 5.5 months of pregnancy and this was likely due to the presence of twin fetuses. Despite targeted therapy of the ensuing retained placenta, the heifer declined in health and had to be euthanized. From the time of diagnosis with hypoparathyroidism until euthanasia (29 months of age), blood levels of calcium, phosphorus and PTH were regularly monitored. Calcium and phosphorus levels varied widely. Serum PTH was consistently undetectable. At postmortem examination, the parathyroid glands could not be located. CONCLUSIONS AND CLINICAL IMPORTANCE: To our knowledge, this is the first report of naturally occurring hypoparathyroidism in cattle and with a clinical presentation of alopecia.

Reversible myocardial failure in a cat with primary hypoparathyroidism.

A 4-year-old domestic shorthair cat presented with tetany. Laboratory testing confirmed severe hypocalcemia and primary hypoparathyroidism. The cat subsequently developed congestive heart failure secondary to myocardial failure and was treated with pimobendan, enalapril, furosemide, calcitriol and calcium salts. All clinical signs resolved and cardiac function returned to normal within 1 month, and remained normal after cessation of all medications except calcitriol. Hypocalcemia-associated cardiomyopathy is a rare, reversible condition that has not previously been reported in a veterinary patient, and it should be considered as a differential diagnosis in patients with myocardial failure.

Primary hypoparathyroidism in dogs: a retrospective study of 17 cases.

OBJECTIVE: To evaluate the clinico-pathological findings, response to treatment and prevalence of complications in dogs with primary hypoparathyroidism. DESIGN: Retrospective study of 17 dogs presenting to the University of Melbourne Veterinary Clinical Centre and Murdoch University Veterinary Hospital over a 15 year period (1990 to 2004). Case records were evaluated for signalment, body weight, diet type, historical and clinical findings, serum total calcium, phosphate, albumin and parathyroid hormone concentrations, urinary fractional excretion ratios of calcium and phosphate, electrocardiogram (ECG) results, treatments administered, outcome and period of follow-up. RESULTS: The most common breeds identified were St Bernard (three dogs), Chihuahua (two dogs), German Shepherd (two dogs) and Jack Russell Terrier (two dogs). Three dogs were cross bred. Seizures, muscle tremors and fasciculations, stiff gait, tetany, muscle cramping, behavioural change and hyperventilation were the most common clinical signs. Vomiting, inappetence, diarrhoea, abdominal pain, hyperthermia, facial pruritus, ataxia, weakness, cataracts, and circling also occurred with less frequency. The mean duration of observed clinical signs preceding diagnosis was 33 days (median 13 days, range 1 to 173 days). All dogs had marked hypocalcaemia with normal or mildly increased serum albumin concentrations. Mean phosphate concentrations were significantly higher in inappetent dogs (P = 0.049). Mean serum calcium concentrations were significantly lower in dogs with cataracts compared to those without (P = 0.046). There were no other significant relationships between serum calcium or phosphate concentrations and the clinical presentation or outcome. No significant correlations were identified between the presence of a particular clinical sign and the duration of clinical signs. ECGs were obtained in four dogs and all exhibited QT interval prolongation due to a ST-segment prolongation. Sixteen of 17 dogs were treated successfully for hypocalcaemia and discharged from hospital. Acute management included parenteral calcium gluconate (10 dogs) and intravenous anticonvulsants (five dogs). Chronic therapy included oral vitamin D analogues and calcium supplementation. Treatment complications occurred in two dogs and included acute renal failure (one dog) and iatrogenic tissue necrosis following subcutaneous calcium administration (one dog). The mean follow-up period was 14.5 months (median 13 months, range 0 to 39 months). Twelve dogs were alive at the last follow up and two dogs were euthanased for unrelated reasons. The type of vitamin D analogue used was not associated with outcome. CONCLUSION: Primary hypoparathyroidism was an uncommon diagnosis in dogs. Saint Bernards, cross bred dogs, German Shepherd dogs and Terrier breeds were most commonly affected. Neurological signs were the most common presenting clinical signs, although alimentary signs may have been more common than previously reported. Dogs with primary hypoparathyroidism appeared to have a good prognosis following initiation of calcium supplementation and vitamin D therapy. Complications of treatment were uncommon and could be minimised with regular monitoring.

Hypocalcaemia due to nutritional calcium deficiency and hypoparathyroidism in an adult dog.

A 13-year-old intact male poodle had suffered periodic tetanic crises for two months. It was cachectic and moderately dehydrated, and during the crises blindness, a stiff gait and behavioural changes were observed. Routine haematological and biochemical profiles showed that it was severely hypocalcaemic, with a corrected plasma calcium concentration of 1.13 mmol/litre (reference range 2.25 to 3 mmol/litre). The dog was fed a home-made diet composed of chicken and basmati rice cooked with a soup bouillon cube; an analysis of its daily allowance indicated that the dog was generally malnourished and received only 0.222 g of calcium per day rather than the 0.6 g it required. In addition, the dog had a low blood concentration of parathyroid hormone of 12 ng/litre (reference range 20 to 80 ng/litre). Supplementing the dog with calcitriol for four days and correcting its diet increased its blood calcium to the lower part of the reference range and resolved the clinical signs, although its parathyroid hormone concentration was still low one year later.

Feline endocrinopathies.

Feline endocrinopathies (excluding diabetes mellitus) include hyperthyroidism, hypothyroidism, acromegaly, hyposomatotropism, diabetes insipidus, hyperadrenocorticism, primary sex hormone-secreting adrenal tumors, primary hyperaldosteronism, pheochromocytoma, hypoadrenocorticism, hyperparathyroidism, and hypoparathyroidism. Each of these conditions will be discussed including their prevalence, cause, clinical signs, diagnosis, treatment options, and prognosis.

Primary hypoparathyroidism in a cat complicated by suspect iatrogenic calcinosis cutis.

An adult male cat presented to the Ontario Veterinary College after having a seizure at the humane society. The cat was diagnosed with primary hypoparathyroidism and was treated with calcium and vitamin D3 supplementation. Calcium supplementation included subcutaneous (SC) administration of diluted calcium gluconate according to protocols described in recent literature. Seven days after SC calcium administration, firm SC masses developed in the intrascapular area where the injections were given and in the dependent axillary area. These areas became raised, formed crusts, necrosed, and left scars. Although not histopathologically confirmed, the author postulates that this was a direct reaction to SC calcium gluconate administration.

Severe calcinosis cutis associated with treatment of hypoparathyroidism in a dog.

A 6-month-old, female border collie was referred for evaluation of hypocalcemia, hyperphosphatemia, fever, and painful ventral abdominal skin. She had recently been treated intravenously and subcutaneously (SC) with a diluted 10% calcium gluconate solution. The medical evaluation supported the diagnosis of primary hypoparathyroidism, but the subsequent hospital course was complicated by severe calcinosis cutis, which caused extensive skin necrosis and marked debilitation. This patient illustrates that administration of a calcium gluconate solution SC can be associated with extensive morbidity when administered to hyperphosphatemic patients.