Hypo- versus hyper-thyroidism in 2 cats: the culprit for miliary dermatitis/hypersensitivity versus growth retardation

Bu olgu sunumunda iki farkli kedide karsilasilan hipotiroidizme karsi hipertiroidizm iliskili farkli klinik bulgular sunuldu. Ilk olgumuz 3 aylik yasta, erkek, short-hair irki yavru kedi olup asiri cucelik sikayeti ile klinigimize getirilmistir. Radyografik bulgularinda uzun kemiklerde epifiziyal disgenezis ve epifiziyal kemiklesmede gecikme tespit edildi. Kongenital hipotiroidzm tanisi dusuk total tiroksin seviyesiyle desteklendi ve levotiroksin ile sagaltima baslanildi. Ikinci olgumuz ise sagaltima ragmen duzelmeyen dermatolojik bulgular ile klinigimize basvurdu. Klinik muayenede alopesi, yaygin kabuklanma ve kil ortusunde matlasma goruldu. Deriden alinan punc biyopsi sonuclari, artan serum total tiroksin ve serbest T4 ve iliskili miliyar dermatitis ile hipertiroidizm tanisi konuldu. Bu olgumuzda metimazol ve hiperimmun sut faktoru baslanildi. Sonuc olarak her iki olgumuzda da erken tani ve sagaltim iliskili klinik bulgularin giderilmesine ve laboratuvar sonuclarina gore normal tiroid fonksiyonlarina kavusmalarina yol acti.


Introduction
Hyperthyroidism, one of the most frequent endocrine disorder in middle to older aged cats (Peterson, 1986;Feldman and Nelson, 1996;Hibbert, 2018), denote excessive production of thyroid hormones due to abnormally functioning thyroidal tissue (Volckaert et al., 2016a). The incidence of hyperthyroidism in cats has been elevated since it was recognized. Regarding hyperthyroid cats, solely 5% of are younger than 10 years of age during initial diagnosis (Mooney, 2010;McLean et al., 2014;Stephens et al., 2014;Scott-Moncrieff, 2015).
Two articles indicated the importance of hyperthyroidism among cats i.e. part I (anatomy, physiology, diagnosis and imagining) (Volckaert et al., 2016a) and part II (scintigraphic diagnosis and relevant treatment (Volckaert et al., 2016b), which prompted the present authors to publish the case series herein. Furthermore the present author's interest was also aroused following receipt of two different cats, 1 with hypo-and the other with hyper-thyroidism with specifical clinical findings and treatment.

Case Report
Case I: hypothyroiditic cat Initial examination revealed disproportional short legs and abducted elbows. As being informed by the owner the cat was obstipated and anorectic. Facial structure of the cat resembled that of a very small aged kitten, although at time of referral it was 3 months of age ( Figure 1). It was also interesting that the cat was mentally dull, with very slow respond to stimuli. The owner also informed that the cat was not playing with toys or its brother belonging to the same litter. The cat was 0.78 kg, even if a normal weight for a domestic shorthair kitten of that age must be around or above 2 kg.

Figure 1. a) Hypothyrodic cat b)
Hypothyroditic cat shown on the right along with her brother which was born on the same litter. Both cats were 3 months of age, whereas the present case was lethargic, showed failure to growth. c) both normal and hypothyroidic cats shown at 7 months of age (2 months of methimazole treatment).
Serum total T4 levels were lower than the reference ranges (0.5 µg/dL; reference range 0.8-4.7µg/dL). Fecal examination was negative and not deemed any parasite. Beside antiparasitic medication was available previously. The cat was prescribed for levothyroxine (0.05 mg q 12 h orally), lactulose (1.5 mL q 8 h orally) along with warm water enema, as was also described previously (Traas et al., 2008).

Case II: cat with hyperthyroidism
The first case was referred to the clinic with unresolved dermatological lesions [(miliary dermatitis, erythema, erosion and crusting) ( Figure  2)]. As being informed by the owner the cat was hypersensitive and referred to several Veterinary Clinics with varying duration of diarrhea, unresponsive to traditional treatment. Up to date there was no precise diagnosis nor thyroidal profile was analyzed. On initial referral the cat was overactive, aggressive, with evidence of   For treatment, methimazole (2,5 mg/cat) and hyperimmune milk factor were applied during two months. Before treatment regime skin punch biopsy (6 mm) was performed. For this, local anesthesia with 0, 3 ml lidocaine 2% was injected by subcutaneously surrounding the selected lesion. After anesthesia, biopsy punch was placed on selected area and observed biopsy samples was transferred to %10 formalin.

Discussion
In the vast majority of cats with hyperthyroidism weight loss, hyperactivity, increased body temperature, diarrhea, cardiovascular problems (tachycardia or other relevant arrhythmias, systolic murmurs, hypertrophic cardiomyopathy, tachypnea, dyspnea), altered behavior, stress intolerance, muscle weakness/ atrophy, hair coat changes, polyuria/polydipsia, systemic hypertension, polyphagia, vomiting, increased frequency of defecation (Bucknell, 2000;Mooney, 2010;Klein, 2012;Peterson, 2014;Scott-Moncrieff, 2015). The atypical form of hyperthyroidism, also known as apathetic or masked hyperthyroidism, is associated with signs of depression and anorexia, often still accompanied by weight loss. It is important to keep in mind that not all hyperthyroid patients demonstrate the typical clinical presentation and signs may be subtle, especially in early stages (Bucknell, 2000). Some of hyperthyroid cats present excessive grooming behavior causing alopecia or crusty rash, accompanied with intense itching resembling miliary dermatitis (Peterson, 2012). The latter condition might be in relation with with an underlying allergy, whereas dermatological alterations could reflect cat's obsessive and compulsive behavior (i.e. elevated licking and grooming) (Peterson, 2011). In one of the present cases herein reported clinical signs mimicking hyperthyroidism were diarrhea, tachycardia and weight loss. Besides striking and interesting clinical feature was miliary dermatitis in which should be on the list of differential diagnosis for hyperthyroidism (Peterson, 2011).
Hyperimmune milk factor (microlactin) was the drug of choice for relieving hypersensitivity and miliary dermatitis in case I of this article. Regarding the efficacy of microlactin; it inhibits and reverses neutrophil attachment to the blood vessel wall-stabilizing inactivated neutrophils unable to participate in inflammation (Beck and Fuhrer, 1993;Okubo et al., 2016). Furthermore it is able to maintain proper actioning of another inflammatory cell, macrophages with proven invitro and invivo effects (Gingerich and Strobel, 2003;Bello and Allen, 2005). Taking into account crusting dermatosis in cats, small circumscribed crusts of feline dermatitis might be found, in which the most commonly observed allergic dermatitis is flea allergy (Carlotti, 2004). There might be also crusts related to excoriations located on to the dorsolumbar area (Carlotti, 2004), which was similar to the case I in this article. Feline eosinophilic plaque (Gross et al., 1986) and miliary dermatitis (Carlotti, 2004) both mimic clinical findings of allergic skin disease, in which dermal inflammation composed of eosinophils, mast cells, lymphocytes and neutrophils (Gross et al., 2005). In the present case with hyperthyroidism, 6 mm skin punch biopsy was performed prior to treatment application, in which histopathology revealed mixed inflammatory infiltrate reach in mast cells along with erosion and ulceration. Therefore, it may be safely suggested that microlactin may have helped clinical recovery and relieving inflammation.
Taking into account growth failure in cats and dogs, related endocrine causes are GH/IGF-1 deficiency, excessive glucocorticoids, hypothyroidism, hypoadrenocorticism, diabetes mellitus and vitamin D disorders (Scott-Moncrieff, 2015). In the present case with hypothyroidism diagnosis was based on low levels of total T4 and fT4, along with normal blood glucose, cortisol and vitamin D levels. Besides early recognition of the disease and effective levothyroxine treatment all resulted in growth of the kitten, which supported precise/tentative diagnosis.
In conclusion the good (well prognosis and respond to treatment), the bad (the clinical signs) and the ugly (serum biomarkers i.e. endocrine profile) parts of two distinct thyroidal disorders; hypo-vs. hyper-thyroidism have been documented herein at the same time. Early recognition, real time diagnosis within the necessary biomarkers and prompt treatment might overcome thyroidal diseases among cats.