Secondary hypothyroidism following head trauma in a cat

Abstract

An 18-month-old female neutered domestic short hair cat was examined because of marked polydipsia and stunted growth following head trauma when it was 8 weeks old. Diagnostic evaluation revealed hyposthenuric urine, low concentrations of thyroid hormone and undetectable thyroid stimulating hormone concentrations which did not rise following thyroid releasing hormone administration. Lateral radiographs of the left and right tibiae revealed incomplete mineralisation of the greater tubercle and open physis. An almost empty sella turcica and a greatly reduced pituitary were visible on magnetic resonance images of the brain. A presumptive diagnosis of secondary hypothyroidism and central diabetes insipidus following head trauma was made.

An 18-month-old female neutered domestic shorthair cat was examined at the Queen's Veterinary School Hospital, University of Cambridge with a history of marked polydipsia since the age of 8 weeks. The polydipsia began immediately after a cupboard door had fallen on the kitten's head. Biochemistry was generally unremarkable and the urine specific gravity was 1.007. Magnetic resonance imaging of the kitten's head revealed an almost empty sella turcica and a very reduced pituitary size (Fig 1a,b). A presumptive diagnosis of traumatically induced central diabetes insipidus was made and the cat had been treated by the referring vet with twice daily placement of one drop of desmopressin (DDAVP 100 μg/ml) into the both lower conjunctivial sacs. The desmopressin therapy reduced the polydipsia although the owner considered the cat to be still drinking excessively. Since the accident, the cat had grown poorly and was considerably smaller than its sibling. The owner's other concern apart from the poor growth and polydipsia was that the cat had vomited intermittently during the previous 2 months.

Fig 1.

(a) T1-weighted parasagittal magnetic resonance image of the cat's brain. Note the small size of the pituitary in an almost empty sella turcica (arrow). (b) T1-weighted transverse magnetic resonance image of the cat's brain at the level of the sella turcica revealing a very reduced pituitary size (arrow indicates small tissue remnant in the sella).

Clinical examination revealed that, although small (2.56 kg), the cat's body proportions appeared normal (Fig 2a). There were permanent teeth although the dentition was poorly developed and covered in tartar (Fig 2b). Haematology was unremarkable. Biochemistry revealed elevated urea (13.3 mmol/l, 6.7–10.0), glucose (7.0 mmol/l, 4.0–5.3), creatinine (233 μmol/l, 45–150), phosphate (1.57 mmol/l, 0.70–1.20), creatine kinase (184 iu/l, 49–151) and calcium (2.44 mmol/l, 1.90–2.40) concentrations. Urine specific gravity was 1.007. Thoracic radiographs revealed a small thorax with to contents to scale and open physes. Abdominal radiographs were unremarkable.

Fig 2.

(a) Appearance of cat at 18 months of age. The cat is poorly grown but has normal body proportions. (b) The cat had permanent teeth although the dentition was poorly developed and covered in tartar.

Adrenocorticotrophic hormone (ACTH) and insulin like growth factor 1 (IGF-1) concentrations were within the reference range and total thyroxine (T₄) concentration was low. Thyroid stimulating hormone (TSH) concentration was undetectably low. Basal plasma cortisol concentrations were undetectable but were normal 1 h after the intravenous administration of 125 mg adrenocorticotrophic hormone (Synacthen; Alliance). Thyroxine concentrations did not appreciably rise and the thyroid stimulating hormone concentration remained undetectable following the intravenous administration of 100 μg thyroid releasing hormone (TRH) (Protirelin; Cambridge Laboratories) (Table 1). The cat's desmopressin treatment was withheld for 24 h and its water intake over the following 14 h was 600 ml. On radiographs of left and right tibiae, there was incomplete mineralisation of the greater tubercle and the physis remained open (Fig 3). The owner was advised to continue the desmopressin treatment and to return for a modified water deprivation study in 5 weeks time.

Table 1.

Endocrine test results (nd: not done)

	Day 1	Day 38	Reference range
Basal thyroxine (nmol/l)	4.6**	<4.0**	19–65
Thyroid stimulating hormone (ng/ml)	<0.10	<0.10	<0.10–0.32
Thyroxine 1 h post-thyroid releasing hormone (nmol/l)	6.7**	nd
Thyroid stimulating hormone 1 h post-thyroid releasing hormone (ng/ml)	<0.10	nd
Thyroxine 4 h post-thyroid releasing hormone (nmol/l)	6.2**	nd
Basal cortisol (nmol/l)	<20	nd	Normal up to 270
Cortisol 1 h post-adrenocorticotrophic hormone stimulation (nmol/l)	243	nd	Normal up to 400
Insulin growth like factor 1 (ng/ml)	235	183	50–1000
Adrenocorticotrophic hormone (pg/ml)	54	89	38–176
Free thyroxine (pmol/l)	nd	<2.0	9.0–30
T4 autoantibodies	nd	0.7	<2.0
T3 autoantibodies	nd	0.6	<2.0

Fig 3.

Lateral radiograph of right and left tibiae at 18 months of age revealing incomplete mineralisation of the tibial tuberosities and open proximal physis.

The cat was re-examined 38 days later. The cat had vomited once since the initial examination and the owner reported that the cat was generally in good health and enjoying a normal quality of life. The cat's water intake remained unchanged, consuming approximately 300 ml of water a day. Total thyroxine, free thyroxine and thyroid stimulating hormone concentrations were all undetectably low and thyroid hormone autoantibodies were within the reference range (Table 1). Adrenocorticotrophic hormone and IGF-1 concentrations were again within the reference range. Urine specific gravity was 1.008. Based on the MRI scans of the brain, the low basal total and free thyroxine concentrations and the failure of thyroxine and thyroid stimulating hormone concentrations to appreciably increase following the intravenous administration of thyroid releasing hormone, a diagnosis of secondary hypothyroidism due to head trauma was made. The exact cause of vomiting was unclear but maybe related to excessive water consumption. The owner elected not to pursue any further investigations into the cause of the vomiting. Because of the requirement to hospitalize the cat for 3 days, the owner did not give consent to perform a modified water deprivation test and the cat was discharged on 0.25 mg L-thyroxine (Soloxine, Arnolds) twice daily and to continue the desmopressin therapy.

The main hormones secreted by the thyroid gland are thyroxine (T₄) and triiodothyronine (T₃). Their principal function is to maintain optimal metabolism in the tissues (Ganong 2001). Thyroid hormone production is controlled by thyroid stimulating hormone produced in the anterior pituitary; the secretion of this tropic hormone is in turn regulated, in part, by thyrotropin releasing hormone from the hypothalamus and is subject to negative feedback control by high circulating levels of thyroid hormones acting on the anterior pituitary and the hypothalamus (Ganong 2001).

Naturally occurring hypothyroidism is an infrequently diagnosed condition in the cat. Hypothyroidism can be classified as primary if the low concentrations of thyroxine are due to thyroid disease or central if pituitary or hypothalamic pathology has lead to low concentrations of TSH and TRH, respectively (Scott-Moncrieff and Guptill-Yoran 2000). Central hypothyroidism can be subclassified into secondary hypothyroidism if inadequate secretion of thyroid stimulating hormone or tertiary if the hypothalamus is secreting insufficient amounts of thyroid releasing hormone. Congenital primary hypothyroidism has been diagnosed in several cats with disproportionate dwarfism and low thyroxine concentrations (Arnold et al 1984, Sjollema et al 1991, Tanase et al 1991, Jones et al 1992). Spontaneous adult onset primary hypothyroidism seems to be uncommon with only one well documented published case (Rand et al 1993, Bruyette 2001). A case of temporary central hypothyroidism was diagnosed in a hydrocephalic cat based on low basal thyroxine concentrations which did not increase to normal levels following thyroid stimulating hormone (Dow et al 1987). To the authors' knowledge, there have been no case reports of secondary hypothyroidism following head trauma in the cat.

In this case, a canine TSH assay was used as a specific feline TSH assay was not available. Canine TSH assays can detect feline TSH and a reference range has been established (Graham et al 2000). Furthermore, TSH concentrations are often reduced in many cases of feline hyperthyroidism and are elevated in most cases following thyroidectomy (Graham et al 2000). Whilst primary or tertiary hypothyroidism could not be definitively ruled out in this case because of the inability of the TSH assay to provide an exact concentration and due to the absence of data on TSH concentrations in normal cats following TRH administration, the low basal total and free thyroxine concentrations and the failure of T₄ and TSH concentrations to increase appreciably following the intravenous administration of TRH is likely to be consistent with secondary hypothyroidism (Sparkes et al 1991, Ramsey et al 1997, Graham et al 2000).

In contrast to cats, hypothyroidism is a common endocrinopathy in dogs. Primary hypothyroidism caused by lymphocytic/plasmacytic thyroiditis is well described in the dog (Scott-Moncrieff and Guptill-Yoran 2000). There have been several case reports describing dogs with central hypothyroidism including a congenital case of hypothyroidism which was considered to be central in origin based on the results of low T₄ concentrations that failed to increase following a single dose of TSH but increased into the reference range following three daily doses of subcutaneous TSH (Mooney and Anderson 1993). Central hypothyroidism has been reported in a family of Giant Schnauzers based on low thyroxine concentrations which entered the normal range after three daily injections of thyroid stimulating hormone (Greco et al 1991). There have been several other case reports of central hypothyroidism in the dog (Neer and Reavis 1983, Barr 1985, Ramsey et al 1999, Kooistra et al 2000).

Cases of central congenital hypothyroidism in dogs and cats with primary congenital hypothyroidism present with similar clinical signs – disproportionate dwarfs with characteristic wide trunks and short legs (Arnold et al 1984, Greco et al 1991, Sjollema et al 1991, Tanase et al 1991, Jones et al 1992, Mooney and Anderson 1993). This is in contrast to this case where the cat was significantly smaller than its littermates but appeared to have normal body proportions. The reason for this is unclear but may be a consequence of normal thyroid function until suffering head trauma. As seen in this case, delayed epiphyseal ossification is a common feature of congenital hypothyroidism in both dogs and cats (Arnold et al 1984, Jones et al 1992, Lieb et al 1997).

In this case, thyroid stimulating hormone may not have been the only pituitary hormone with disturbed secretion following the head trauma incident. The owner did not give consent for a water deprivation test so the precise reason for the polydipsia remains unclear although it is possible that the cat had central diabetes insipidus since the polydipsia started following pituitary damage, the urine was hyposthenuric and the volume of water that the cat was drinking reduced following treatment with desmopressin (Greens and Farrow 1974, Harb et al 1996, Pittari 1996). However, pyschogenic polydipsia could not be ruled out in this case because a water deprivation test was not performed (Taylor 2000). Panhypopituitarism, defined as a complete failure of the pituitary to produce significant concentrations of any hormones, is unlikely in this case since the cat had repeated ACTH and IGF-1 concentrations that were within the reference range. FSH and LH secretion may have been impaired in this case following the head trauma as the cat's uterus and ovaries were poorly developed when the cat was spayed at 6 months of age. However, as FSH and LH concentrations were not measured this remains speculative.

Pituitary dysfunction following head trauma has only been reported occasionally in veterinary medicine. An 11-month-old Miniature Schnauzer which suffered severe head injury was diagnosed with secondary hypoadrenocorticism. The dog had normal serum concentrations of thyroid stimulating hormone and insulin growth like factor 1 (Platt et al 1999). Transient, traumatically induced diabetes insipidus has also been reported in a dog following a road traffic accident (Authement et al 1989). In contrast, pituitary disorders after head injuries in humans have been well described (Emerson 1985, Benvenga et al 2000, Segal-Lieberman et al 2000, Vernet et al 2001, Geffner 2002, Minutti and Zimmerman 2002, Ozdemir et al 2002). One study reviewed 367 cases of hypopituitarism, defined as two or more deficiencies in pituitary hormones, secondary to head trauma and observed that thyroid stimulating hormone was low in 44.3% of cases (Benvenga et al 2000).